Single Nucleotide Polymorphisms in 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase (CYP27B1) Gene : The Risk of Malignant Tumors and Other Chronic Diseases
Latacz, Maria ; Snarska, Jadwiga ; Kostyra, Elżbieta ; Fiedorowicz, Ewa ; Savelkoul, Huub F.J. ; Grzybowski, Roman ; Cieślińska, Anna - \ 2020
Nutrients 12 (2020)3. - ISSN 2072-6643
breast cancer - chronic diseases - colorectal cancer - CYP27B1 - multiple sclerosis - prostate cancer - single nucleotide polymorphism - vitamin D
: Vitamin D is widely known for its roles in the promotion of apoptosis and differentiation, with simultaneous inhibition of proliferation, inflammation, angiogenesis, invasion, and metastasis. Modern literature lacks complete information on polymorphisms in CYP27B1, the only enzyme capable of vitamin D activation. This review presents gathered data that relate to genetic variants in CYP27B1 gene in correlation to multiple diseases, mostly concerning colorectal, prostate, breast, lung, and pancreatic cancers, as well as on other pathologies, such as non-Hodgkin's lymphoma, oral lichen planus, or multiple sclerosis.
Genomic Regions Associated With Skeletal Type Traits in Beef and Dairy Cattle Are Common to Regions Associated With Carcass Traits, Feed Intake and Calving Difficulty
Doyle, Jennifer L. ; Berry, Donagh P. ; Veerkamp, Roel F. ; Carthy, Tara R. ; Walsh, Siobhan W. ; Evans, Ross D. ; Purfield, Deirdre C. - \ 2020
Frontiers in Genetics Livestock Genomics 11 (2020). - ISSN 1664-8021
cattle - genome-wide association study - linear type traits - sequence - single nucleotide polymorphism - skeletal
Linear type traits describing the skeletal characteristics of an animal are moderately to strongly genetically correlated with a range of other performance traits in cattle including feed intake, reproduction traits and carcass merit; thus, type traits could also provide useful insights into the morphological differences among animals underpinning phenotypic differences in these complex traits. The objective of the present study was to identify genomic regions associated with five subjectively scored skeletal linear traits, to determine if these associated regions are common in multiple beef and dairy breeds, and also to determine if these regions overlap with those proposed elsewhere to be associated with correlated performance traits. Analyses were carried out using linear mixed models on imputed whole genome sequence data separately in 1,444 Angus, 1,129 Hereford, 6,433 Charolais, 8,745 Limousin, 1,698 Simmental, and 4,494 Holstein-Friesian cattle, all scored for the linear type traits. There was, on average, 18 months difference in age at assessment of the beef versus the dairy animals. While the majority of the identified quantitative trait loci (QTL), and thus genes, were both trait-specific and breed-specific, a large-effect pleiotropic QTL on BTA6 containing the NCAPG and LCORL genes was associated with all skeletal traits in the Limousin population and with wither height in the Angus. Other than that, little overlap existed in detected QTLs for the skeletal type traits in the other breeds. Only two QTLs overlapped the beef and dairy breeds; both QTLs were located on BTA5 and were associated with height in both the Angus and the Holstein-Friesian, despite the difference in age at assessment. Several detected QTLs in the present study overlapped with QTLs documented elsewhere that are associated with carcass traits, feed intake, and calving difficulty. While most breeding programs select for the macro-traits like carcass weight, carcass conformation, and feed intake, the higher degree of granularity with selection on the individual linear type traits in a multi-trait index underpinning the macro-level goal traits, presents an opportunity to help resolve genetic antagonisms among morphological traits in the pursuit of the animal with optimum performance metrics.
A genetic linkage map of Pleurotus tuoliensis integrated with physical mapping of the de novo sequenced genome and the mating type loci
Gao, Wei ; Qu, Jibin ; Zhang, Jinxia ; Sonnenberg, A.S.M. ; Chen, Qiang ; Zhang, Yan ; Huang, Chenyang - \ 2017
S22027 - linkage mapping - physical mapping - 2b-RAD approach - genotyping by sequencing - single nucleotide polymorphism - mating type loci
Background: Pleurotus tuoliensis (Bailinggu) is a commercially cultivated mushroom species with an increasing popularity in China and other Asian countries. Commercial profits are now low, mainly due to a low yield, long cultivation period and sensitivity to diseases. Breeding efforts are thus required to improve agronomical important traits. Developing saturated genetic linkage and physical maps is a start for applying genetic and molecular approaches to accelerate the precise breeding programs. Results: Here we present a genetic linkage map for P. tuoliensis constructed by using 115 haploid monokaryons derived from a hybrid strain H6. One thousand one hundred and eighty-two SNP markers developed by 2b-RAD (type IIB restriction-site associated DNA) approach were mapped to 12 linkage groups. The map covers 1073 cM with an average marker spacing of 1.0 cM. The genome of P. tuoliensis was de novo sequenced as 40.8 Mb and consisted of 500 scaffolds (>500 bp), which showed a high level of colinearity to the genome of P. eryngii var. eryngii. A total of 97.4% SNP markers (1151) were physically localized on 78 scaffolds, and the physical length of these anchored scaffolds were 33.9 Mb representing 83.1% of the whole genome. Mating type loci A and B were mapped on separate linkage groups and identified physically on the assembled genomes. Five putative pheromone receptors and two putative pheromone precursors were identified for the mating type B locus. Conclusions: This study reported a first genetic linkage map integrated with physical mapping of the de novo sequenced genome and the mating type loci of an important cultivated mushroom in China, P. tuoliensis. The de novo sequenced and annotated genome, assembled using a 2b-RAD generated linkage map, provides a basis for marker-assisted breeding of this economic important mushroom species.
Development and application of a 20K SNP array in potato
Vos, Peter - \ 2016
Wageningen University. Promotor(en): Richard Visser; Fred van Eeuwijk, co-promotor(en): Herman van Eck. - Wageningen : Wageningen University - ISBN 9789462579569 - 166
solanum tuberosum - potatoes - genotypes - single nucleotide polymorphism - data analysis - plant breeding - linkage disequilibrium - genome analysis - tetraploidy - solanum tuberosum - aardappelen - genotypen - single nucleotide polymorphism - gegevensanalyse - plantenveredeling - verstoord koppelingsevenwicht - genoomanalyse - tetraploïdie
In this thesis the results are described of investigations of various application of genome wide SNP (single nucleotide polymorphism) markers. The set of SNP markers was identified by GBS (genotyping by sequencing) strategy. The resulting dataset of 129,156 SNPs across 83 tetraploid varieties was used directly to map traits, but also as a basis for the development of a 20K SNP array in Potato (Solanum tuberosum L.). Subsequently this array, named SolSTW, was used to collect genotypic data from 569 potato genotypes. This dataset offered insight in the breeding history of potato, population structure, linkage disequilibrium (LD) and the potential of GWAS (genome wide association studies) in potato.
In Chapter 2 we describe to development of the SolSTW 20K Infinium SNP array. One third of the SNPs on this array originate from the well-known SolCAP 8303 SNP array. The other SNPs are a subset from a targeted re-sequencing project of 83 tetraploid potato varieties. Because of the high SNP density in potato only a limited number of SNPs is suitable for assay development on a SNP array. An obvious outcome is that flanking SNPs contribute to assay failure, particularly for assays with SNPs located in introns. We used fitTetra software to cluster the distribution of captured signals of each marker into the expected five genotypic classes (nulliplex, simplex, duplex, triplex, quadruplex), resulting in a dataset with 14,530 SNP markers. Subsequently the genotypic data obtained with the SolSTW array was used to characterize a set of 569 potato varieties, advanced breeding clones and progenitors. This resulted in the identification of several footprints of potato breeding. Firstly SNPs were dated i.e. the year of market release of the first variety showing polymorphism for a SNP locus is an indication of the ancestry of a SNP. In such a way we identified SNPs with an ancestry tracing back to heirloom varieties, and SNPs (post-1945 SNPs) tracing back to wild species used in modern introgression breeding. Secondly, the changes in allele frequency were calculated over time. Most SNPs show a relative stable allele frequency over time, and very limited genetic variation is removed from the gene-pool of potato i.e genetic erosion is almost absent. Therefore we conclude that 100 years of breeding has not been able to get rid of non-beneficial genetic variation. Only a limited number of SNPs show a rapid increased in allele frequency, which can be explained by positive selection for disease resistance by breeders, or the more frequent use of several founders.
Better understanding of the genome wide decay of Linkage Disequilibrium (LD) and population structure offers relevant knowledge to perform and interpret the results of a genome wide association study (GWAS) (Chapter 3). Linkage disequilibrium (LD) is a complex phenomenon, and the influence of the factors shaping LD in tetraploids is hardly studied. Therefore we used simulated data to disentangle and therewith understand often-confounded factors underlying LD-decay. We simulated datasets differing in number of haplotypes in a population, and differing in percentage of haplotype specific SNPs. In these simulations we observed that the choice of an estimator of LD-decay has a major effect on the outcome of an LD-decay estimate, while the true LD-decay remains the same. Based on the simulation we conclude that a 90% percentile and a so-called D1/2 (the distance where 50% of the initial LD is decayed) performed best to estimate and compare LD-decay in potato. To understand the various aspects of LD-decay in the variety panel of 537 varieties, the panel was subdivided in several groups based on the age of a variety and the population structure groups. This resulted in the identification of LD-decay over time, i.e in relatively young varieties the average size of the LD-blocks is smaller. The differences between subpopulations were smaller and are most likely the effect of the population structure. We also observed that there are very long LD-blocks caused by introgression breeding and that different a priori MAF-thresholds also can influence the outcome of LD-decay estimation.
Having both LD-decay and population structure defined a genome wide association study (GWAS) was conducted (Chapter 4). For this purpose α-solanine and α-chaconine were measured in potato tubers. Subsequently the sum of both (total SGA) and the ratio between the two were used to discover QTLs for these traits in a GWAS. Additionally we used three bi-parental populations to validate the GWAS results. Total SGA content was confounded with population structure and therefore it was difficult to explain all phenotypic variation with SNP markers. Two QTLs (Sgt1.1 and Sgt11.1) were identified which could be validated in one of the segregating populations. The ratio between α-solanine and α-chaconine was not confounded with population structure, resulted in the identification of two major-effect QTLs (Sgr7.1 & Sgr8.1) located near the candidate genes SGT1 and SGT2, which are known for being responsible in the final steps towards either α-solanine or α-chaconine. The QTL Sgr8.1 could be validated, however similar phenotypes were explained by different haplotypes in two populations. We show that population structure, low frequent alleles and genetic heterogeneity may explain to some degree the missing heritability in GWAS in potato.
In Chapter 5 we describe how the method of graphical genotyping, which is widely used in diploid bi-parental populations, can be applied in a variety panel of tetraploid varieties. We show that a few discrete filtering steps in Excel can be used to display patterns that are visual representations of introgression segments and the locations of historical recombination events. Using this method we identified introgression segments from Solanum vernei including the Gpa5 locus on chromosome 5 and Solanum stoloniferum introgression segment including a gene involved in resistance to Potato Virus Y on chromosome 11. This method requires that the haplotypes that cause the phenotypic effect have to be identical by descent (IBD).
In the final chapter 6 the results of chapter 2 to 5 are discussed. We look forward on how our results can be used in future research and applied in marker-assisted breeding. Additionally some new GWAS results are presented for tuber flesh colour, foliage maturity and resistance to Globodera pallida pathotype 3.
Genetic analysis of within-litter variation in piglets’ birth weight using genomic or pedigree relationship matrices
Sell, E.B. ; Wang, Q. ; Mulder, H.A. ; Knol, E.F. - \ 2015
Journal of Animal Science 93 (2015)4. - ISSN 0021-8812 - p. 1471 - 1480.
generalized linear-models - single nucleotide polymorphism - environmental variance - broiler-chickens - residual variance - individual birth - breeding values - parameters - heterogeneity - selection
The objective of this study was to estimate the genetic variance for within-litter variation of birth weight (BW0) using genomic (GRM) or pedigree relationship matrices (PRM) and to compare the accuracy of estimated breeding values (EBV) for within-litter variation of BW0 using GRM and PRM. The BW0 and residual variance of BW0 were modeled by the double hierarchical generalized linear model using GRM or PRM. Data came from 2 dam lines: Landrace and Large White. After editing, the data set in Landrace consisted of 748 sows with 1,938 litters and 29,430 piglets and in Large White of 989 sows with 3,320 litters and 51,818 piglets. To construct GRM, 46,466 (Landrace) and 44,826 (Large White) single nucleotide polymorphisms were used, whereas to construct PRM, 5 generations of pedigree were used. The accuracy of EBV with GRM was estimated with 8-fold cross-validation and compared to PRM. Estimated variance components were highly similar for GRM and PRM. The maternal genetic variance in residual variance of BW0 in Landrace was 0.05 with GRM and 0.06 with PRM. In Large White these were 0.04 with GRM and 0.05 with PRM. The genetic coefficient of variation (GCVSDe) was about 0.10 in both dam lines. This indicates a change of 10% in residual SD of BW0 when achieving a genetic response of 1 genetic standard deviation. The genetic correlation between birth weight and its residual variance was about 0.6 in both dam lines. The accuracies of selection for within-litter variation of birth weight were 0.35 with GRM and 0.23 with PRM in Landrace and 0.29 with GRM and 0.34 with PRM in Large White. In this case, using GRM did not significantly increase accuracies of selection. Results, however, show good opportunities to select for reduced within-litter variation of BW0. Genomic selection can increase accuracy of selection when reference populations contain at least 2,000 sows
Structural variations in pig genomes
Paudel, Y. - \ 2015
Wageningen University. Promotor(en): Martien Groenen, co-promotor(en): Ole Madsen; Hendrik-Jan Megens. - Wageningen : Wageningen University - ISBN 9789462572171 - 204
varkens - dierveredeling - genomen - genomica - single nucleotide polymorphism - dna-sequencing - fenotypische variatie - chromosoomafwijkingen - evolutie - soortvorming - pigs - animal breeding - genomes - genomics - single nucleotide polymorphism - dna sequencing - phenotypic variation - chromosome aberrations - evolution - speciation
Paudel, Y. (2015). Structural variations in pig genomes. PhD thesis, Wageningen University, the Netherlands
Structural variations are chromosomal rearrangements such as insertions-deletions (INDELs), duplications, inversions, translocations, and copy number variations (CNVs). It has been shown that structural variations are as important as single nucleotide polymorphisms (SNPs) in regards to phenotypic variations. The general aim of this thesis was to use next generation sequencing data to improve our understanding of the evolution of structural variations such as CNVs, and INDELs in pigs. We found that: 1) the frequency of copy number variable regions did not change during pig domestications but rather reflected the demographic history of pigs. 2) CNV of olfactory receptor genes seems to play a role in the on-going speciation of the genus Sus. 3) Variation in copy number of olfactory receptor genes in pigs (Sus scrofa) seems to be shaped by a combination of selection and genetic drift, where the clustering of ORs in the genome is the major source of variation in copy number. 4) Analysis on short INDELs in the pig genome shows that the level of purifying selection of INDELs positively correlates with the functional importance of a genomic region, i.e. strongest purifying selection was observed in gene coding regions. This thesis provides a highly valuable resource for copy number variable regions, INDELs, and SNPs, for future pig genetics and breeding research. Furthermore, this thesis discusses the limitations and improvements of the available tools to conduct structural variation analysis and insights into the future trends in the detection of structural variations.
Conservation genetics of local and wild pig populations : insight in genetic diversity and demographic history
Herrero Medrano, J. - \ 2013
Wageningen University. Promotor(en): Martien Groenen, co-promotor(en): Richard Crooijmans; Hendrik-Jan Megens. - S.l. : s.n. - ISBN 9789461737519 - 160
wilde varkens - sus scrofa - varkens - dna - genetische diversiteit - genetische bronnen van diersoorten - genomica - fylogenetica - zoögeografie - populatiedynamica - single nucleotide polymorphism - wildbescherming - wild pigs - sus scrofa - pigs - dna - genetic diversity - animal genetic resources - genomics - phylogenetics - zoogeography - population dynamics - single nucleotide polymorphism - wildlife conservation
Het doel van het onderzoek zoals beschreven in dit proefschrift was om de genetische diversiteit en demografische geschiedenis van lokale varkenspopulaties te verkennen middels het integreren van verschillende genetische merker systemen.
Genomics in de fokkerij: in tien jaar van topwetenschap naar big business
Arendonk, J.A.M. van; Groenen, M. - \ 2013
Kennis Online 10 (2013)mei. - p. 7 - 8.
dierveredeling - genomica - fokkerijmethoden - moleculaire technieken - single nucleotide polymorphism - selectiemethoden - melkvee - varkens - genomen - animal breeding - genomics - animal breeding methods - molecular techniques - single nucleotide polymorphism - selection methods - dairy cattle - pigs - genomes
Genomics was tien jaar geleden topwetenschap die alleen bedreven werd in dure laboratoria van universiteiten en onderzoeksinstituten. Nu gebruiken fokbedrijven DNA-chips om al op jonge leeftijd te kunnen voorspellen welke stier het beste sperma levert, en om te zien of berengeur bij varkens door een slim fokprogramma kan worden voorkomen.
Use of SNP markers to conserve genome-wide genetic diversity in livestock
Engelsma, K.A. - \ 2012
Wageningen University. Promotor(en): Johan van Arendonk, co-promotor(en): Jack Windig. - S.l. : s.n. - ISBN 9789461733863 - 178
dierveredeling - rundvee - single nucleotide polymorphism - genetische diversiteit - genomen - genomica - conservering - animal breeding - cattle - single nucleotide polymorphism - genetic diversity - genomes - genomics - conservation
Conservation of genetic diversity in livestock breeds is important since it is, both within and between breeds, under threat. The availability of large numbers of SNP markers has resulted in new opportunities to estimate genetic diversity in more detail, and to improve prioritization of animals for conservation of genetic diversity. The aim of this thesis was to further explore the potential of SNP markers for estimation and conservation of genetic diversity within livestock breeds. This was evaluated analyzing Holstein cattle populations, genotyped with a commonly used 50k SNP chip. Genetic diversity was estimated with SNP markers and compared to genetic diversity estimated with pedigree information. Both methods could detect differences in overall genetic diversity, even between two closely related populations. With SNP markers, differences in genetic diversity at the chromosomal level could be identified as well. Subsequently, SNP markers and pedigree information were used to prioritize animals for conservation in a gene bank using optimal contributions. SNP based prioritization was slightly more effective than pedigree based information, both over the whole genome and at specific regions of the genome. We extended the optimal contribution method to simultaneously conserve a single allele at a specific frequency and maximize the overall genetic diversity conserved in a gene bank. The loss of overall genetic diversity was larger when the target frequency for animals conserved in the gene bank differed more from the original frequency in the population. It can be concluded that dense SNP data form a powerful tool for estimation and conservation of genetic diversity in livestock breeds. Although pedigree information gives a good representation of the overall genetic diversity, SNP markers can provide more detailed information about the genetic diversity over the genome. Especially for small populations, SNP markers can play an important role in conservation of unique alleles, while simultaneously minimizing the loss of genetic diversity at the rest of the genome.
Genetic dissection of drought tolerance in potato
Anithakumari, A.M. - \ 2011
Wageningen University. Promotor(en): Richard Visser, co-promotor(en): Gerard van der Linden. - [S.l.] : S.n. - ISBN 9789085858379 - 152
solanum tuberosum - aardappelen - droogteresistentie - genetische analyse - diploïdie - single nucleotide polymorphism - genetische merkers - kwantitatieve kenmerken - loci voor kwantitatief kenmerk - genetische kartering - plantenveredeling - solanum tuberosum - potatoes - drought resistance - genetic analysis - diploidy - single nucleotide polymorphism - genetic markers - quantitative traits - quantitative trait loci - genetic mapping - plant breeding
Drought is the most important cause of crop and yield loss around the world. Breeding for
drought tolerance is not straightforward, as drought is a complex trait. A better understanding
of the expression of drought traits, the genes underlying the traits and the way these genes
interact will significantly increase the success of breeding for drought tolerance.
Potato is an important food crop, yet it is relatively susceptible to drought. As a first step
towards identifying the genetic basis for drought tolerance in potato, we make use of diploid
potato populations that have been genetically well characterized (CxE, SHxRH). The CxE
population was extensively evaluated for drought tolerance in vitro and for two successive
years (2008, 2009) under greenhouse conditions and the data were used for QTL mapping.
For optimal QTL mapping, we expanded the CxE and SHxRH genetic maps with 499 SNP
markers (two arrays 384 and 768SNP arrays respectively, enriched for putative stress
tolerance candidate genes). The SNPs were discovered in public EST databases using
QualitySNP software and detected with the Illumina GoldenGate assay. About 300 SNPs
served as bridge markers between the CxE and SHxRH maps. This will enable us to make use
of the extensive genetic and sequence information of the SHxRH population and the RH
genome sequence. With the availability of the potato genome sequence of the doubled
monoploid DM1-3 516R44 (DM) (www.potatogenome.net), it was possible to further
examine the SNP marker loci for paralogs and intron spanning sequences. In total 732 SNP
marker loci were found to be unique in the potato genome sequence. Many of these SNP
markers not only served as landmarks on the genetic map but may also as putative genes
underlying quantitative traits. In addition the validated SNP markers are now utilized as
anchors in the potato physical map.
We investigated the possibility of screening potato for relevant drought traits in in vitro
cultures and evaluated the CxE population for the response to PEG-induced water deficit
stress and recovery potential after stress. Significant genetic variation was observed for the
response to drought and for recovery potential. Several shoot and root growth traits were
measured. In this study the genetic variation and heritability estimates were high to very high
for the measured traits under control and recovery condition. In total 23 QTLs were detected
in plants under control, stress and recovery treatments. Interesting putative candidate genes
that may underly stress response QTLs were identified.
The drought tolerance evaluation of the CxE population in pots in the greenhouse included
traits like leaf Relative Water Content, δ13C as a measure of Water Use Efficiency,
Chlorophyll Fluorescence, Chlorophyll Content, shoot and root biomass and tuber yield. The
progeny displayed a wide contrast for drought tolerance, with individuals surviving and
recovering completely after 3 weeks of drought, and others completely wilted beyond
recovery. Most of the traits had high heritabilities. QTLs effective in multiple treatments and
years were detected for tuber number, tuber weight, plant height, shoot fresh and dry weight.
Other QTLs were found to be dependent on the environment: QTL x Environment interaction
was found for leaf d13C under drought conditions and we speculate that the function of δ13C
was genetically split into a stomatal and non-stomatal component.
Many of the QTLs for growth traits measured both in the greenhouse and in in vitro cultures
were specific to either of the growth conditions. Yet significant QTLs that were detected for
plant height, shoot dry weight, fresh biomass for plants grown in the greenhouse were also
found when the population was grown in vitro. These QTLs may be less affected by
environmental influences, and we may therefore expect that some of these QTLs will be
relevant under field conditions as well. This also suggests that the in vitro system may be used
for preliminary selection in breeding programmes for specific performance-related traits.
The genetic architecture of transcript-level variation for drought response was captured in the
potato population CxE and mapped as expression QTLs (eQTLs). We anchored the
differentially expressed genes to the genome sequence of potato, and this enabled us to
determine whether the transcription of these genes (the eQTLs) is in cis or in trans regulated.
The combined use of genome-wide detection of eQTLs in combination with genome sequence
information for gene location has enables us to detect regulatory hot spots for drought
response in the CxE population. Based on gene ontology annotation, a number of eQTLs were
detected for genes known to be involved in drought signal transduction and drought-induced
transcriptional regulation, and for redox genes. Examination of co-localization of eQTLs and
phenotypic QTLs identified several interesting eQTLs for genes that may be involved in
specifying the phenotypic QTL, for instance, the eQTL for a gene that was annotated with a
putative function in the photosystem II light reaction colocalized with trait QTL of
chlorophyll florescence (Fv/Fm) on chromosome 1, along with other genes involved in 139
drought response such as heat shock proteins and signaling proteins with known induced
expression under stress conditions. On chromosome 10, eQTLs for genes involved in carbon
partitioning, signaling receptor kinases, transcription factors and hormone and lipid
metabolism were colocalized with phenotypic QTLs for chlorophyll content and stomatal
component of δ13C. As we have only touched the surface of the information contained in the
transcriptome dataset combined with the phenotyping data, continued efforts on mining the
dataset and in depth analysis will most likely reveal more putative candidate genes for QTL
This thesis constitutes the first knowledge of in vitro and greenhouse screening for drought
tolerance in potato and has led to the description of important traits for screening and
selection in breeding for drought tolerance. The QTLs identified in this thesis may be
interesting targets for potato breeding to improve drought tolerance of the potato crop.
Furthermore, our results illustrate the power of application of integrated genetic and genomics
approaches to unravel the molecular components underlying abiotic stress tolerance traits.
Bioinformatics' approaches to detect genetic variation in whole genome sequencing data
Kerstens, H.H.D. - \ 2010
Wageningen University. Promotor(en): Martien Groenen; Mari Smits. - [S.l. : S.n. - ISBN 9789085857808 - 182
bio-informatica - genomen - nucleotidenvolgordes - genetische variatie - varkens - kalkoenen - kippen - anas platyrhynchos - dierveredeling - genexpressieanalyse - single nucleotide polymorphism - marker assisted breeding - bioinformatics - genomes - nucleotide sequences - genetic variation - pigs - turkeys - fowls - anas platyrhynchos - animal breeding - genomics - single nucleotide polymorphism - marker assisted breeding
Current genetic marker repositories are not sufficient or even are completely lacking for most farm animals. However, genetic markers are essential for the development of a research tool facilitating discovery of genetic factors that contribute to resistance to disease and the overall welfare and performance in farm animals.
By large scale identification of Single Nucleotide Polymorphisms (SNPs) and Structural Variants (SVs) we aimed to contribute to the development of a repository of genetic variants for farm animals. For this purpose bioinformatics data pipelines were designed and validated to address the challenge of the cost effective identification of genetic markers in DNA sequencing data even in absence of a fully sequenced reference genome.
To find SNPs in pig, we analysed publicly available whole genome shotgun sequencing datasets by sequence alignment and clustering. Sequence clusters were assigned to genomic locations using publicly available BAC sequencing and BAC mapping data. Within the sequence clusters thousands of SNPs were detected of which the genomic location is roughly known.
For turkey and duck, species that both were lacking a sufficient sequence data repository for variant discovery, we applied next-generation sequencing (NGS) on a reduced genome representation of a pooled DNA sample. For turkey a genome reference was reconstructed from our sequencing data and available public sequencing data whereas in duck the reference genome constructed by a (NGS) project was used. SNPs obtained by our cost-effective SNP detection procedure still turned out to cover, at intervals, the whole turkey and duck genomes and are of sufficient quality to be used in genotyping studies. Allele frequencies, obtained by genotyping animal panels with a subset our SNPs, correlated well with those observed during SNP detection. The availability of two external duck SNP datasets allowed for the construction of a subset of SNPs which we had in common with these sets. Genotyping turned out that this subset was of outstanding quality and can be used for benchmarking other SNPs that we identified within duck.
Ongoing developments in (NGS) allowed for paired end sequencing which is an extension on sequencing analysis that provides information about which pair of reads are coming from the outer ends of one sequenced DNA fragment. We applied this technique on a reduced genome representation of four chicken breeds to detect SVs. Paired end reads were mapped to the chicken reference genome and SVs were identified as abnormally aligned read pairs that have orientation or span sizes discordant from the reference genome. SV detection parameters, to distinguish true structural variants from false positives, were designed and optimized by validation of a small representative sample of SVs using PCR and traditional capillary sequencing.
To conclude: we developed SNP repositories which fulfils a requirement for SNPs to perform linkage analysis, comparative genomics QTL studies and ultimately GWA studies in a range of farm animals. We also set the first step in developing a repository for SVs in chicken, a relatively new genetic marker in animal sciences.
Differences in genetic diversity in Holstein cattle with high and low genetic merit
Engelsma, K.A. ; Veerkamp, R.F. ; Calus, M.P.L. ; Windig, J.J. - \ 2010
zwartbont - genetische diversiteit - fokwaarde - melkproductie - afkomst - verwantschap - single nucleotide polymorphism - moleculaire merkers - holstein-friesian - genetic diversity - breeding value - milk production - ancestry - kinship - single nucleotide polymorphism - molecular markers
Evaluations of genetic diversity in Holstein cattle based on pedigree data, indicate a decrease in genetic diversity in Holstein cattle, because of a lower effective population size and a higher relatedness compared to other cattle breeds. However, pedigree based diversity reflects only the overall genetic diversity, while for specific regions on the genome the genetic diversity might be completely different. The objective in this study was to compare genetic diversity across the genome between Holstein cattle with high and low genetic merit for milk production, using pedigree information and SNP data.
Genetic analysis of production, immunity and behaviour in laying hens
Biscarini, F. - \ 2010
Wageningen University. Promotor(en): Johan van Arendonk, co-promotor(en): Jan van der Poel; Henk Bovenhuis. - [S.l. : S.n. - ISBN 9789085857860 - 132
genetische analyse - hennen - eierproductie - immuniteit - diergedrag - dierveredeling - fokwaarde - heritability - immuniteitsreactie - single nucleotide polymorphism - genetic analysis - hens - egg production - immunity - animal behaviour - animal breeding - breeding value - heritability - immune response - single nucleotide polymorphism
The new regulations about the husbandry of laying hens and the so-called genomic revolution offer both opportunities and challenges for the breeding of layers. Hens are currently housed mainly in battery cages of 4 individuals each. Following recent developments of the communitarian legislation, many countries will soon adopt furnished cages or non-cage systems, which will lead to larger groups of hens. Also, beak-trimming will be prohibited in EU countries in the near future. Advancements in sequencing technology are making an always greater number of genetic markers available at increasingly cheaper prices, making genome-wide studies possible and helping geneticists to start unraveling the mystery of the genetic make-up of animals, which until a few years ago was considered a black-box. This thesis touches upon the impact of such innovations on the breeding of laying hens.
Use of pooled data in the genetic evaluation of laying hens
Hens are usually housed in cages and therefore pooled instead of individual egg records are often available: a pooled egg record is the total production of a cage, when the egg production of the individual hens is unknown. Current selection schemes are carried out in nucleus herds where hens are housed individually, so that egg production of individual birds can be recorded and used for genetic evaluations. Based on this information sires and dams are selected. Such a selection scheme based on individually housed hens introduces a discrepancy between the environment where hens are selected and the environment in which hens are kept for commercial egg production (group housing). Selecting animals in one environment and using them in a different environment might lead to genotype x environment interaction (Besbes and Ducroq, 2003), thereby reducing the realized response to selection. Future husbandry conditions, with larger groups of hens or hens housed in furnished cages might make this problem even worse. A method to use pooled data in the genetic evaluation of laying hens would therefore be of interest. In Chapters 2 and 3 of this thesis it is described how to use pooled records for the estimation of heritability and breeding values. In chapter 2 the use of individual and pooled observations is compared. Individual body weights of hens at different ages were available: these were then pooled by cage in order to create pooled records. Heritabilities estimated from pooled and individual data correlated well: the standard error of estimates based on pooled records was however about twice that of estimates based on individual records. The accuracy of EBVs from pooled data is lower than the accuracy of EBVs from individual data; in the case of sires with at least 10 offspring the reduction in accuracy was about 23%. This loss of precision in estimating genetic parameters and breeding values is understandable considering that pooled records are a less detailed of information. However, this lower accuracy should be interpreted in the context of direct vs indirect selection. The breeding goal is the trait under commercial conditions (group housing), and if testing is under individual housing, the genetic correlation between group and individual housing is relevant. The ratio of the selection response for direct and indirect selection is a function of the accuracies for both situations, the standard deviations of the traits and the genetic correlation between the traits (Falconer, 1989). Similarly, the ratio between accuracies based on pooled and individual data provides a threshold for the genetic correlation between individual and group housing below which pooled data would result in a greater selection response. In practical breeding also the costs of individual housing relative to the costs of group housing are relevant. Since group housing is cheaper than individual housing, more selection candidates could be tested for the same level of costs. This would in turn result in higher selection intensity and larger response to selection.
In chapter 3 the method of analyzing pooled data developed in chapter 2 was compared with an approximation consisting in assigning cage means to each hen in a cage, then treating them as individual observations. Cross-validation was used to compare the two methods: the method developed in Chapter 2 performed consistently better than the approximate method in terms of predicting ability.
In the general discussion, finally, it was described how to estimate genetic and phenotypic correlations from pooled data.
Across-line association studies for immune response and feather pecking behaviour
The great number of genetic markers available at increasingly lower prices has been fostering developments in genomic research. Association studies between genetic markers and phenotypes are typically conducted within populations (breeds, or lines): the amount of LD conserved in a population is exploited using high marker density, such as SNP chips, and markers relatively close to QTLs are expected to show significant effects in association studies. In this thesis we propose to take it one step further and perform association studies across lines. This requires higher marker density but increases the resolution. The amount of LD conserved across lines is expected to be lower than within lines and the phase of the marker-phenotype association might be different in the different lines. On the other hand markers that happen to show significant effects in an across-line association study are likely to be close to the QTL. These issues in conducting marker-phenotype association studies across populations were addressed in Chapters 4 and 5 of this thesis, where it was shown how to deal with multiple populations when analyzing hens from 9 different genetic lines of White Leghorn and Rhode Island Red origin genotyped for a panel of 1536 SNP (Single Nucleotide Polymorphism) markers.
The traits analysed were immunological parameters and plumage damage due to feather pecking behaviour, two classes of traits for which, given that they have relatively low heritability and are difficult and expensive to measure, genomic information may be particularly valuable. Immunological parameters might be used in selection programmes aimed at improving disease resistance of laying hens, while information on the genetic background of feather pecking behaviour can be useful in reducing problems due to this behavioural disorder of layers. Under future husbandry conditions susceptibility to infectious diseases and feather pecking are expected to become more serious problems: both aspects of layer production are in fact related to the number of individuals that interact with each other, which will increase as a result of the application of the EU directive 1999/74/EC. In addition, the ban of beak-trimming will make it more difficult to control the consequences of feather pecking (plumage damage, cannibalism, mortality). Genetic selection might represent an appealing addition to the current control measures. The association studies identified several regions of interest. The gene for interleukin 17 (IL17), on chromosome 3, was found to be associated with natural and acquired antibody titres, and with the classical and alternative pathways of complement activation. The major histocompatibility complex (MHC) genes on chromosome 16 showed significant association with natural and acquired antibody titres and classical complement activity. The interleukin 12B gene (IL12B) on chromosome 13 was associated with natural antibody titres. As for feather pecking behaviour, a role of the gene for the serotonin receptor 2C (HTR2C) on chromosome 4 was found. This supports existing evidence of a prominent involvement of the serotonergic system in the modulation of this behavioural disorder in laying hens. The genes for IL9, IL4, CCL4 and NFKB were found to be associated to plumage condition, revealing relationships between the immune system and behaviour.
Review of the initial validation and characterization of a chicken 3K SNP array.
Muir, W.M. ; Wong, G.K. ; Zhang, Y. ; Wang, J. ; Groenen, M.A.M. ; Crooijmans, R.P.M.A. ; Zhang, H.M. ; McKay, J. ; McLeod, C.W. ; Okimoto, R. - \ 2008
Worlds Poultry Science Journal 64 (2008). - ISSN 0043-9339 - p. 219 - 226.
dierveredeling - genetische bronnen van diersoorten - kippen - pluimvee - biodiversiteit - genetica - genetische kartering - dna - dna-sequencing - genotypen - genetische diversiteit - kippenrassen - single nucleotide polymorphism - animal breeding - animal genetic resources - fowls - poultry - biodiversity - genetics - genetic mapping - dna - dna sequencing - genotypes - genetic diversity - fowl breeds - single nucleotide polymorphism
In 2004 the chicken genome sequence and more than 2.8 million single nucleotide polymorphisms (SNPs) were reported. This information greatly enhanced the ability of poultry scientists to understand chicken biology, especially with respect to identification of quantitative trait loci (QTL) and genes that control simple and complex traits. To validate and address the quality of the reported SNPs, assays for 3072 SNPS were developed and used to genotype 2576 DNAs isolated from commercial and experimental birds. Over 90% of the SNPs were valid based on the criterion used for segregating, and over 88% had a minor allele frequency of 2% or greater. As the East Lansing (EL) and Wageningen University (WAU) reference panels were genotyped, 1933 SNPs were added to the chicken genetic map, which was used in the second chicken genome sequence assembly. It was also discovered that linkage disequilibrium varied considerably between commercial layers and broilers; with the latter having haplotype blocks averaging 10 to 50 kb in size. Finally, it was estimated that commercial lines have lost 70% or more of their genetic diversity, with the majority of allele loss attributable to the limited number of chicken breeds used.
Genome-wide assessment of worldwide chicken SNP genetic diversity indicates significant absence of rare alleles in commercial breeds
Muir, W.M. ; Wong, G.K. ; Zhang, Y. ; Groenen, M.A.M. ; Crooijmans, R.P.M.A. ; Megens, H.J.W.C. - \ 2008
Proceedings of the National Academy of Sciences of the United States of America 105 (2008)45. - ISSN 0027-8424 - p. 17312 - 17317.
dierveredeling - pluimvee - rassen (dieren) - dierlijke productie - biodiversiteit - genetische diversiteit - allelen - inteelt - genotyping - single nucleotide polymorphism - animal breeding - poultry - breeds - animal production - biodiversity - genetic diversity - alleles - inbreeding - genotyping - single nucleotide polymorphism - linkage disequilibrium - population-structure - myostatin gene - polymorphism - phenotype - selection - mutation - growth - cattle
Breed utilization, genetic improvement, and industry consolidation are predicted to have major impacts on the genetic composition of commercial chickens. Consequently, the question arises as to whether sufficient genetic diversity remains within industry stocks to address future needs. With the chicken genome sequence and more than 2.8 million single-nucleotide polymorphisms (SNPs), it is now possible to address biodiversity using a previously unattainable metric: missing alleles. To achieve this assessment, 2551 informative SNPs were genotyped on 2580 individuals, including 1440 commercial birds. The proportion of alleles lacking in commercial populations was assessed by (1) estimating the global SNP allele frequency distribution from a hypothetical ancestral population as a reference, then determining the portion of the distribution lost, and then (2) determining the relationship between allele loss and the inbreeding coefficient. The results indicate that 50% or more of the genetic diversity in ancestral breeds is absent in commercial pure lines. The missing genetic diversity resulted from the limited number of incorporated breeds. As such, hypothetically combining stocks within a company could recover only preexisting within-breed variability, but not more rare ancestral alleles. We establish that SNP weights act as sentinels of biodiversity and provide an objective assessment of the strains that are most valuable for preserving genetic diversity. This is the first experimental analysis investigating the extant genetic diversity of virtually an entire agricultural commodity. The methods presented are the first to characterize biodiversity in terms of allelic diversity and to objectively link rate of allele loss with the inbreeding coefficient
A bioinformatics approach to marker development
Tang, J. - \ 2008
Wageningen University. Promotor(en): Jack Leunissen, co-promotor(en): Ben Vosman. - [S.l.] : S.n. - ISBN 9789085048114 - 150
bio-informatica - genetische merkers - merkergenen - nucleotidenvolgordes - moleculaire genetica - algoritmen - loci voor kwantitatief kenmerk - microsatellieten - single nucleotide polymorphism - bioinformatics - genetic markers - marker genes - nucleotide sequences - molecular genetics - algorithms - quantitative trait loci - microsatellites - single nucleotide polymorphism
The thesis focuses on two bioinformatics research topics: the development of tools for an efficient and reliable identification of single nucleotides polymorphisms (SNPs) and polymorphic simple sequence repeats (SSRs) from expressed sequence tags (ESTs) (Chapter 2, 3 and 4), and the subsequent implementation of these tools in a pipeline for narrowing down QTL intervals to facilitate the identification of candidate genes for the QTL (Chapter 5).
Chapter 1 provides an introduction to molecular markers, SNP and SSR markers, illustrated by a number of applications of molecular markers, as well as existing programs for their detection.
After analysis of existing problems and programs for the detection SNPs, a new algorithm is described to reliably identify SNPs and indels in EST data from diploid and polyploid species (Chapter 2). The algorithm is implemented in a program called QualitySNP. This program uses three filters to identify reliable SNPs: filter one screens for potential SNPs by requiring at least two sequences per represented allele; filter two uses a haplotype-based strategy to filter out clusters with paralogs and false SNPs caused by sequence errors; finally, filter three calculates a confidence score for every putative SNP according to the number of occurrences of each allele in high and low quality regions.
For the detection of non-synonymous SNPs (nsSNP), synonymous SNPs and SNPs in UTRs, a program was developed as well. Furthermore, these programs were implemented in a pipeline that includes the identification of SNPs and nsSNPs, as well as a storage and retrieval system. Using this pipeline, large numbers of SNPs could be identified in potato ESTs. QualitySNP is available for running on LINUX and UNIX systems; the program, user manual and examples are available at http://www.bioinformatics.nl/tools/snpweb/ .
Chapter 3 describes a web-based implementation of the QualitySNP algorithm, called HaploSNPer, which is a tool for the detection of alleles and SNPs in user-specified input sequences from both diploid and polyploid species. HaploSNPer tries to find homologous sequences in user-specified sequence databases using a user-supplied seed sequence, or in a collection of input sequences. All alleles and associated SNPs are identified on clusters of these homologous sequences using QualitySNP. HaploSNPer provides a user-friendly interface for visualization of SNPs and alleles, which allows the selection of informative SNPs and allele specific makers. Currently HaploSNPer is available for nine animal and thirteen plant species, and is available from http://www.bioinformatics.nl/tools/haplosnper/ .
Chapter 4 presents a new tool, called PolySSR, to identify polymorphic SSRs rather than just SSRs based on public EST sequence data derived from heterozygotes and/or different genotypes. Based on PolySSR a pipeline was developed to automatically develop primers for putatively polymorphic SSR markers, taking into account SNPs in the SSR flanking regions, thus improving the success rate of the potential markers. Furthermore, SSR positions in coding or UTR regions of genes are identified by the pipeline. The pipeline also includes a searchable database for these SSRs.
The value of PolySSR was demonstrated by the fact that nearly all tested SSRs predicted to be polymorphic were indeed validated as polymorphic, and also most designed primers produced clear amplicons. Large numbers of polymorphic SSRs were identified from publicly available ESTs in potato, tomato, rice, Arabidopsis, brassica and chicken using the pipeline. They are stored into a database, which is available at http://www.bioinformatics.nl/tools/polyssr/ . PolySSR not only decreases the cost of designing and testing primers, it also brings a new approach to use the redundancy and heterozygosity of ESTs for developing SSRs that was ignored before. Analysis of the data obtained with polySSR showed that a larger percentage of short SSRs identified in the species used in the study were polymorphic than that of long SSRs. From this it is clear that in the past we have ‘forgotten’ a whole class of putatively informative markers.
QualitySNP and PolySSR have been implemented into a pipeline called GeneTagger to find candidate genes underlying a QTL using the strategy of narrowing the QTL interval (Chapter 5). The pipeline first detects the syntenic region of a QTL interval in the species under study in a model species based on marker sequences linked to the QTL. Next, within the syntenic regions identified in the model species genes are identified that might have a function related to the QTL or genes within the regions that are not part of a large gene family. Based on their map position in the model species a number of genes are selected for marker development. To facilitate marker development, ESTs derived from the target species are analyzed using QualitySNP, PolySSR and other tools. Based on identified genetic variations in the selected genes, molecular markers can be developed for accurate fine-mapping of the QTL and ultimately identification of the gene underlying the QTL effect. The pipeline has been used to narrow the clubroot resistance QTL. The tool is available from the website http://www.bioinformatics.nl/tools/genetagger/ .
Finally, merits and shortcomings of the tools that have been developed as well as related bioinformatics questions that arose during these studies are discussed in Chapter 6.
Phylogenetic relationships within the phylum Nematoda as revealed by ribosomal DNA, and their biological implications
Holterman, M.H.M. - \ 2007
Wageningen University. Promotor(en): Jaap Bakker, co-promotor(en): Hans Helder. - [S.l.] : S.n. - ISBN 9789085048800 - 208
nematoda - ribosomaal dna - fylogenetica - klassering volgens erfelijke eigenschappen - fylogenie - plantenparasitaire nematoden - vrijlevende nematoden - dorylaimidae - chromadoridae - tylenchidae - zeenematoden - single nucleotide polymorphism - nematoda - ribosomal dna - phylogenetics - cladistics - phylogeny - plant parasitic nematodes - free living nematodes - dorylaimidae - chromadoridae - tylenchidae - marine nematodes - single nucleotide polymorphism
Nematodes – “eel worms”; members of the phylum Nematoda – can be considered as a success story within the Metazoa (multicellular, heterotrophic eukaryotes in which cells lack cell walls): they are speciose and – probably - the most numerous group of multicellular animals on our planet. Nematodes are present in virtually all terrestrial, freshwater and marine habitats. Nematodes are trophically diverse; they may feed on bacteria, fungi/oomycetes, algae and protozoa, other nematodes or on a combination of these (omnivores), or live as facultative or obligatory parasites of plants or animals. As they are abundant, ubiquitous and occupy several trophic levels, they play an important role in the soil food web. Nematode parasites of animals affect billions of humans and livestock, while plant parasites such as cyst, root knot and lesion nematodes cause large agricultural losses worldwide.
Despite their undisputed ecological and economical relevance, the systematics of the phylum Nematoda is far from established. One of the aims of this research was to further elucidate nematode phylogeny using molecular data. First a phylogenetic tree was constructed of 349 taxa, spanning the entire phylum Nematoda, on the basis of full length small subunit ribosomal DNA (SSU rDNA) sequences. A series of mostly well-supported bifurcations defined twelve major clades, whereas the most basal clade was defined by representatives of the Enoplida and Triplonchida. Our analysis confirmed the paraphyly of the Adenophorea. Furthermore it was found that the SSU rDNA from representatives of the distal clades evolved at a higher rate than the SSU rDNA from the basal clades. In the meantime, a substantial number of sequences was added to our overall SSU rDNA nematode alignment - both public data (GenBank) and data generated by ourselves (≈ 1,500 sequences in total; February 2008). It is noted that the clade division as proposed in 2006 on the basis of “only” 349 taxa still seems to be valid.
Subsequent research focused on three specific groups; Dorylaimia, Chromadoria and Tylenchomorpha. Within the suborder Dorylaimina, the SSU rDNA provided an exceptionally low phylogenetic signal, and - therefore – a part (≈ 1,000 bp) of the more variable large subunit ribosomal DNA (LSU rDNA) was analyzed. In most cases nematode relationships could be elucidated with good support, although some areas in the trees remained unresolved. Generally speaking the results of molecular phylogenetics corresponded fairly well with classical nematode taxonomy. The main exception was the order Dorylaimida where twelve subclades could be distinguished which bore little resemblance to classical taxonomy. Furthermore the suitability of ribosomal DNA for a (semi-) quantative molecular identification method was demonstrated using quantitative PCR (q-PCR) and primers designed to specifically amplify members of the order Mononchida and the potato cyst nematodes Globodera pallida and G. rostochiensis.
Plant parasitism has arisen several times within the phylum Nematoda (once in the Triplonchida, at least three times in the Dorylaimida and at least twice in the Tylenchomorpha). The long-standing and generally accepted hypothesis states that plant parasites evolved from fungal feeding ancestors. However, while in most cases plant parasites were associated with fungal feeding nematodes, this hypothesis could neither be confirmed nor denied with the results of our phylogenetic analyses. In the case of two Dorylaimida (Pungentus and Longidorella), however, the ancestor was probably an omnivore. The analysis of this problem was substantially hampered by the lack of knowledge on feeding behavior of basal Tylenchomorpha.
Presumably, the common ancestor of the nematodes lived in a marine environment and - if this assumption is correct - the transition to a limnoterrestrial environment must have taken place at least once. Surprisingly, analysis of the Chromadoria (minus the Rhabditida) revealed that transitions from a thalassic to a limnoterrestrial habitat (and vice versa) have taken place at least 11 times in the Chromadoria. Given their frequency these transitions are apparently fairly easy to achieve for nematodes and the possible adaptations involved were discussed.
Nematodes vary widely in their responses to environmental disturbance, making them good bio-indicators of soil health. Yet it is not known with certainty which traits are responsible for tolerance to stress in nematodes. A framework was laid out to study correlations between nematode traits and stress tolerance. Furthermore the importance of accounting for the confounding effects of phylogeny was demonstrated. This is a first step towards a transparent, ecological grouping of free-living nematodes.
It is worthwhile mentioning that - on the basis of the rDNA-based molecular framework described in this PhD thesis - DNA sequences signatures were identified for nearly all North-West European terrestrial and freshwater nematodes families. The relationship between quantitative PCR signal and numbers of individuals has been established for nearly all families and a first testing of DNA barcode-based community analysis is planned for spring 2008.
Estimation of the extent of linkage disequilibrium in seven regions of the porcine genome
Jungerius, B.J. ; Gu, J. ; Crooijmans, R.P.M.A. ; Poel, J.J. van der; Groenen, M.A.M. ; Oost, B.A. van; Pas, M.F.W. te - \ 2005
Animal Biotechnology 16 (2005)1. - ISSN 1049-5398 - p. 41 - 54.
single nucleotide polymorphism - human lipoprotein-lipase - sequence variation - populations - genes - locus
Linkage disequilibrium (LD) refers to the correlation among neighboring alleles, reflecting non-random patterns of association between alleles at (nearby) loci. A better understanding of LD in the porcine genome is of direct relevance for identification of genes and mutations with a certain effect on the traits of interest. Here, 215 SNPs in seven genomic regions were genotyped in individuals of three breeds. Pairwise linkage disequilibrium was calculated for all marker pairs. To estimate the extent of LD, all pairwise LD values were plotted against the distance between the markers. Based on SNP markers in four genomic regions analyzed in three panels from populations of Large White, Dutch Landrace, and Meishan origin, useful LD is estimated to extend for approximately 40 to 60 kb in the porcine genome
Leptin gene polymorphisms and their phenotypic associations
Lende, T. van der; Pas, M.F.W. te; Veerkamp, R.F. ; Liefers, S.C. - \ 2005
Vitamins and Hormones-Advances in Research and Applications 71 (2005). - ISSN 0083-6729 - p. 373 - 404.
human ob gene - human obese gene - binding protein-alpha - single nucleotide polymorphism - hypoxia-inducible factor-1 - 5' untranslated region - body-mass index - ob/ob mice - missense mutation - adipose-tissue
In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin gene polymorphisms have drawn much attention in biomedical research. Leptin gene polymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically important production and reproduction traits. Of the polymorphisms reported for exonic, intronic, and promoter regions of the leptin gene, 16 have been included in association studies in humans, 19 in cattle, and 6 (all exonic or intronic) in pigs. In humans, associations have been found with overweight or (early-onset) obesity, non-insulin-dependent diabetes mellitus, prostate cancer, and non-Hodgkin’s lymphoma. In cattle, associations have been found with feed intake, milk yield traits, carcass traits, and reproduction-related traits, and in pigs with feed intake, average daily gain, carcass traits (backfat/leanness), and reproduction performance traits. Many of the polymorphisms were only included in a limited number of association studies, or the phenotypes studied varied largely for a given polymorphism between studies. Therefore, many of the associations found for these polymorphisms need to be confirmed in future studies before firm conclusions can be drawn.