Genomic divergence of zebu and taurine cattle identified through high-density SNP genotyping

Background

Natural selection has molded evolution across all taxa. At an arguable date of around 330,000 years ago there were already at least two different types of cattle that became ancestors of nearly all modern cattle, the Bos taurus taurus more adapted to temperate climates and the tropically adapted Bos taurus indicus. After domestication, human selection exponentially intensified these differences. To better understand the genetic differences between these subspecies and detect genomic regions potentially under divergent selection, animals from the International Bovine HapMap Experiment were genotyped for over 770,000 SNP across the genome and compared using smoothed F_ST. The taurine sample was represented by ten breeds and the contrasting zebu cohort by three breeds.

Results

Each cattle group evidenced similar numbers of polymorphic markers well distributed across the genome. Principal components analyses and unsupervised clustering confirmed the well-characterized main division of domestic cattle. The top 1% smoothed F_ST, potentially associated to positive selection, contained 48 genomic regions across 17 chromosomes. Nearly half of the top F_ST signals (n = 22) were previously detected using a lower density SNP assay. Amongst the strongest signals were the BTA7:~50 Mb and BTA14:~25 Mb; both regions harboring candidate genes and different patterns of linkage disequilibrium that potentially represent intrinsic differences between cattle types. The bottom 1% of the smoothed F_ST values, potentially associated to balancing selection, included 24 regions across 13 chromosomes. These regions often overlap with copy number variants, including the highly variable region at BTA23:~24 Mb that harbors a large number of MHC genes. Under these regions, 318 unique Ensembl genes are annotated with a significant overrepresentation of immune related pathways.

Conclusions

Genomic regions that are potentially linked to purifying or balancing selection processes in domestic cattle were identified. These regions are of particular interest to understand the natural and human selective pressures to which these subspecies were exposed to and how the genetic background of these populations evolved in response to environmental challenges and human manipulation.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-14-876) contains supplementary material, which is available to authorized users.     

Detection of selection signatures in dairy and beef cattle using high-density genomic information

Background

Artificial selection for economically important traits in cattle is expected to have left distinctive selection signatures on the genome. Access to high-density genotypes facilitates the accurate identification of genomic regions that have undergone positive selection. These findings help to better elucidate the mechanisms of selection and to identify candidate genes of interest to breeding programs.

Results

Information on 705 243 autosomal single nucleotide polymorphisms (SNPs) in 3122 dairy and beef male animals from seven cattle breeds (Angus, Belgian Blue, Charolais, Hereford, Holstein-Friesian, Limousin and Simmental) were used to detect selection signatures by applying two complementary methods, integrated haplotype score (iHS) and global fixation index (F_ST). To control for false positive results, we used false discovery rate (FDR) adjustment to calculate adjusted iHS within each breed and the genome-wide significance level was about 0.003. Using the iHS method, 83, 92, 91, 101, 85, 101 and 86 significant genomic regions were detected for Angus, Belgian Blue, Charolais, Hereford, Holstein-Friesian, Limousin and Simmental cattle, respectively. None of these regions was common to all seven breeds. Using the F_ST approach, 704 individual SNPs were detected across breeds. Annotation of the regions of the genome that showed selection signatures revealed several interesting candidate genes i.e. DGAT1, ABCG2, MSTN, CAPN3, FABP3, CHCHD7, PLAG1, JAZF1, PRKG2, ACTC1, TBC1D1, GHR, BMP2, TSG1, LYN, KIT and MC1R that play a role in milk production, reproduction, body size, muscle formation or coat color. Fifty-seven common candidate genes were found by both the iHS and global F_ST methods across the seven breeds. Moreover, many novel genomic regions and genes were detected within the regions that showed selection signatures; for some candidate genes, signatures of positive selection exist in the human genome. Multilevel bioinformatic analyses of the detected candidate genes suggested that the PPAR pathway may have been subjected to positive selection.

Conclusions

This study provides a high-resolution bovine genomic map of positive selection signatures that are either specific to one breed or common to a subset of the seven breeds analyzed. Our results will contribute to the detection of functional candidate genes that have undergone positive selection in future studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0127-3) contains supplementary material, which is available to authorized users.     

TagSNP transferability and relative loss of variability prediction from HapMap to an admixed population

Background

The application of a subset of single nucleotide polymorphisms, the tagSNPs, can be useful in capturing untyped SNPs information in a genomic region. TagSNP transferability from the HapMap dataset to admixed populations is of uncertain value due population structure, admixture, drift and recombination effects. In this work an empirical dataset from a Brazilian admixed sample was evaluated against the HapMap population to measure tagSNP transferability and the relative loss of variability prediction.

Methods

The transferability study was carried out using SNPs dispersed over four genomic regions: the PTPN22, HMGCR, VDR and CETP genes. Variability coverage and the prediction accuracy for tagSNPs in the selected genomic regions of HapMap phase II were computed using a prediction accuracy algorithm. Transferability of tagSNPs and relative loss of prediction were evaluated according to the difference between the Brazilian sample and the pooled and single HapMap population estimates.

Results

Each population presented different levels of prediction per gene. On average, the Brazilian (BRA) sample displayed a lower power of prediction when compared to HapMap and the pooled sample. There was a relative loss of prediction for BRA when using single HapMap populations, but a pooled HapMap dataset generated minor loss of variability prediction and lower standard deviations, except at the VDR locus at which loss was minor using CEU tagSNPs.

Conclusion

Studies that involve tagSNP selection for an admixed population should not be generally correlated with any specific HapMap population and can be better represented with a pooled dataset in most cases.     

Investigation of the genetic diversity of domestic Capra hircus breeds reared within an early goat domestication area in Iran

Background

Iran is an area of particular interest for investigating goat diversity. Archaeological remains indicate early goat domestication (about 10 000 years ago) in the Iranian Zagros Mountains as well as in the high Euphrates valley and southeastern Anatolia. In addition, mitochondrial DNA data of domestic goats and wild ancestors (C. aegagrusor bezoar) suggest a pre-domestication management of wild populations in southern Zagros and central Iranian Plateau. In this study genetic diversity was assessed in seven Iranian native goat breeds, namely Markhoz, Najdi, Taleshi, Khalkhali, Naini, native Abadeh and Turki-Ghashghaei. A total of 317 animals were characterized using 14 microsatellite loci. Two Pakistani goat populations, Pahari and Teddy, were genotyped for comparison.

Results

Iranian goats possess a remarkable genetic diversity (average expected heterozygosity of 0.671 across loci, 10.7 alleles per locus) mainly accounted for by the within-breed component (G_ST = 5.9%). Positive and highly significant F_IS values in the Naini, Turki-Ghashghaei, Abadeh and Markhoz breeds indicate some level of inbreeding in these populations. Multivariate analyses cluster Iranian goats into northern, central and western groups, with the western breeds relatively distinct from the others. Pakistani breeds show some relationship with Iranian populations, even if their position is not consistent across analyses. Gene flow was higher within regions (west, north, central) compared to between regions but particularly low between the western and the other two regions, probably due to the isolating topography of the Zagros mountain range. The Turki-Ghashghaei, Najdi and Abadeh breeds are reared in geographic areas where mtDNA provided evidence of early domestication. These breeds are highly variable, located on basal short branches in the neighbor-joining tree, close to the origin of the principal component analysis plot and, although highly admixed, they are quite distinct from those reared on the western side of the Zagros mountain range.

Conclusions

These observations call for further investigation of the nuclear DNA diversity of these breeds within a much wider geographic context to confirm or re-discuss the current hypothesis (based on maternal lineage data) of an almost exclusive contribution of the eastern Anatolian bezoar to the domestic goat gene pool.     

A genome-wide detection of selection signatures in conserved and commercial pig breeds maintained in Poland

Background

Identification of selection signatures can provide a direct insight into the mechanism of artificial selection and allow further disclosure of the candidate genes related to the animals’ phenotypic variation. Domestication and subsequent long-time selection have resulted in extensive phenotypic changes in domestic pigs, involving a number of traits, like behavior, body composition, disease resistance, reproduction and coat color. In this study, based on genotypes obtained from PorcineSNP60 Illumina assay we attempt to detect both diversifying and within-breed selection signatures in 530 pigs belonging to four breeds: Polish Landrace, Pu?awska, Z?otnicka White and Z?otnicka Spotted, of which the last three are a subject of conservative breeding and substantially represent the native populations.

Results

A two largely complementary statistical methods were used for signatures detection, including: pairwise F_ST and relative extended haplotype homozygosity (REHH) test. Breed-specific diversifying selection signals included several genes involved in processes connected with fertility, growth and metabolism which are potentially responsible for different phenotypes of the studied breeds. The diversifying selection signals also comprised PPARD gene that was previously found to have a large effect on the shape of the external ear in pigs or two genes encoding neuropeptide Y receptors (Y2 and Y5) involved in fat deposition and stress response which are important features differentiating the studied breeds. REHH statistics allowed detecting several within-breed selection signatures overlapping with genes connected with a range of functions including, among others: metabolic pathways, immune system response or implantation and development of the embryo.

Conclusions

The study provides many potential candidate genes with implication for traits selected in the individual breeds and gives strong basis for further studies aiming at identification of sources of variation among the studied pig breeds.

     

Assessing The Spatial Dependence of Adaptive Loci in 43 European and Western Asian Goat Breeds Using AFLP Markers

Background

During the past decades, neutral DNA markers have been extensively employed to study demography, population genetics and structure in livestock, but less interest has been devoted to the evaluation of livestock adaptive potential through the identification of genomic regions likely to be under natural selection.

Methodology/Principal findings

Landscape genomics can greatly benefit the entire livestock system through the identification of genotypes better adapted to specific or extreme environmental conditions. Therefore we analyzed 101 AFLP markers in 43 European and Western Asian goat breeds both with Matsam software, based on a correlative approach (SAM), and with Mcheza and Bayescan, two F_ST based software able to detect markers carrying signatures of natural selection.Matsam identified four loci possibly under natural selection – also confirmed by F_ST-outlier methods – and significantly associated with environmental variables such as diurnal temperature range, frequency of precipitation, relative humidity and solar radiation.

Conclusions/Significance

These results show that landscape genomics can provide useful information on the environmental factors affecting the adaptive potential of livestock living in specific climatic conditions. Besides adding conservation value to livestock genetic resources, this knowledge may lead to the development of novel molecular tools useful to preserve the adaptive potential of local breeds during genetic improvement programs, and to increase the adaptability of industrial breeds to changing environments.     

Signatures of selection in sheep bred for resistance or susceptibility to gastrointestinal nematodes

Background

Gastrointestinal nematodes are one of the most serious causes of disease in domestic ruminants worldwide. There is considerable variation in resistance to gastrointestinal nematodes within and between sheep breeds, which appears to be due to underlying genetic diversity. Through selection of resistant animals, rapid genetic progress has been demonstrated in both research and commercial flocks. Recent advances in genome sequencing and genomic technologies provide new opportunities to understand the ovine host response to gastrointestinal nematodes at the molecular level, and to identify polymorphisms conferring nematode resistance.

Results

Divergent lines of Romney and Perendale sheep, selectively bred for high and low faecal nematode egg count, were genotyped using the Illumina® Ovine SNP50 BeadChip. The resulting genome-wide SNP data were analysed for selective sweeps on loci associated with resistance or susceptibility to gastrointestinal nematode infection. Population differentiation using F_ST and Peddrift revealed sixteen regions, which included candidate genes involved in chitinase activity and the cytokine response. Two of the sixteen regions identified were contained within previously identified QTLs associated with nematode resistance.

Conclusions

In this study we identified fourteen novel regions associated with resistance or susceptibility to gastrointestinal nematodes. Results from this study support the hypothesis that host resistance to internal nematode parasites is likely to be controlled by a number of loci of moderate to small effects.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-637) contains supplementary material, which is available to authorized users.     

Detecting selection signatures in three Iranian sheep breeds

The objective of genome mapping is to achieve valuable insight into the connection between gene variants (genotype) and observed traits (phenotype). Part of that objective is to understand the selective forces that have operated on a population. Finding links between genotype–phenotype changes makes it possible to identify selective sweeps by patterns of genetic variation and linkage disequilibrium. Based on Illumina 50KSNP chip data, two approaches, XP‐EHH (cross‐population extend haplotype homozygosity) and F_ST (fixation index), were carried out in this research to identify selective sweeps in the genome of three Iranian local sheep breeds: Baluchi (n = 86), Lori‐Bakhtiari (n = 45) and Zel (n = 45). Using both methods, 93 candidate genomic regions were identified as harboring putative selective sweeps. Bioinformatics analysis of the genomic regions showed that signatures of selection related to multiple candidate genes, such as HOXB9, HOXB13, ACAN, NPR2, TRIL, AOX1, CSF2, GHR, TNS2, SPAG8, HINT2, ALS2, AAAS, RARG, SYCP2, CAV1, PPP1R3D, PLA2G7, TTLL7 and C20orf10, that play a role in skeletal system and tail, sugar and energy metabolisms, growth, reproduction, immune and nervous system traits. Our findings indicated diverse genomic selection during the domestication of Iranian sheep breeds.     

Genome‐wide detection of signatures of selection in Korean Hanwoo cattle

The Korean Hanwoo cattle have been intensively selected for production traits, especially high intramuscular fat content. It is believed that ancient crossings between different breeds contributed to forming the Hanwoo, but little is known about the genomic differences and similarities between other cattle breeds and the Hanwoo. In this work, cattle breeds were grouped by origin into four types and used for comparisons: the Europeans (represented by six breeds), zebu (Nelore), African taurine (N'Dama) and Hanwoo. All animals had genotypes for around 680 000 SNPs after quality control of genotypes. Average heterozygosity was lower in Nelore and N'Dama (0.22 and 0.21 respectively) than in Europeans (0.26–0.31, with Shorthorn as outlier at 0.24) and Hanwoo (0.29). Pairwise F_ST analyses demonstrated that Hanwoo are more related to European cattle than to Nelore, with N'Dama in an intermediate position. This finding was corroborated by principal components and unsupervised hierarchical clustering. Using genome‐wide smoothed F_ST, 55 genomic regions potentially under positive selection in Hanwoo were identified. Among these, 29 were regions also detected in previous studies. Twenty‐four regions were exclusive to Hanwoo, and a number of other regions were shared with one or two of the other groups. These regions overlap a number of genes that are related to immune, reproduction and fatty acid metabolism pathways. Further analyses are needed to better characterize the ancestry of the Hanwoo cattle and to define the genes responsible to the identified selection peaks.     

Genetic diversity of two native sheep breeds by genome-wide analysis of single nucleotide polymorphisms

Wallachian and Sumava sheep are autochthonous breeds that have undergone a significant bottleneck effect and subsequent restoration efforts. The first objective of this study was to evaluate the degree of genetic variability of both breeds and, therefore, the current management of the breeding. The second was to determine whether these two breeds still retain their genetic uniqueness in relation to each other and other breeds, despite regenerative interventions. Our data consisted of 48 individuals of Sumava and 37 individuals of Wallachian sheep. The comparison data contained 25 other breeds (primarily European) from the HapMap dataset generated by the International Sheep Genomics Consortium. When comparing all 27 breeds, the Czech breeds clustered with 15 other breeds and formed a single branch with them according to Nei's distances. At the same time, however, the clusters of both breeds were integral and easily distinguishable from the others when displayed with principal component analysis (PCA). Population substructure analysis did not show any common genetic ancestry of the Czech national breeds and breeds used for regeneration or, eventually, breeds whose ancestral population was used for regeneration. The average values of F_ST were higher in Wallachian sheep (F_ST = 0.14) than in Sumava sheep (F_ST = 0.08). The linkage disequilibrium (LD) extension per autosome was higher in Wallachian than in Sumava sheep. Consequently, the N_e estimates five generations ago were 68 for Sumava versus 34 for Wallachian sheep. Both native Czech breeds exhibit a wide range of inbreeding based on the excess of homozygosity (F_HOM) among individuals, from ?0.04 to 0.16 in Sumava and from ?0.13 to 0.12 in Wallachian. Average inbreeding based on runs of homozygosity was 0.21 in Sumava and 0.27 in Wallachian. Most detected runs of homozygosity (ROH) were less than 5 Mb long for both breeds. ROH segments longer than 15 Mb were absent in Wallachian sheep. Concerning putative selection signatures, a total of 471 candidate genes in Wallachian sheep within 11 hotspots and 653 genes within 13 hotspots in Sumava sheep were identified. Czech breeds appear to be well differentiated from each other and other European breeds. Their genetic diversity is low, especially in the case of the Wallachian breed. Sumava is not so threatened by low diversity but has a larger share of the non-native gene pool.     

A genome scan for selection signatures in Taihu pig breeds using next-generation sequencing

Taihu pig breeds are the most prolific breeds of swine in the world, and they also have superior economic traits, including high resistance to disease, superior meat quality, high resistance to crude feed and a docile temperament. The formation of these phenotypic characteristics is largely a result of long-term artificial or natural selection. Therefore, exploring selection signatures in the genomes of the Taihu pigs will help us to identify porcine genes related to productivity traits, disease and behaviour. In this study, we used both intra-population (Relative Extend Haplotype Homozygosity Test (REHH)) and inter-population (the Cross-Population Extend Haplotype Homozygosity Test (XPEHH); F-STATISTICS, F_ST) methods to detect genomic regions that might be under selection process in Taihu pig breeds. As a result, we found 282 (REHH) and 112 (XPEHH) selection signature candidate regions corresponding to 159.78 Mb (6.15%) and 62.29 Mb (2.40%) genomic regions, respectively. Further investigations of the selection candidate regions revealed that many genes under these genomic regions were related to reproductive traits (such as the TLR9 gene), coat colour (such as the KIT gene) and fat metabolism (such as the CPT1A and MAML3 genes). Furthermore, gene enrichment analyses showed that genes under the selection candidate regions were significantly over-represented in pathways related to diseases, such as autoimmune thyroid and asthma diseases. In conclusion, several candidate genes potentially under positive selection were involved in characteristics of Taihu pig. These results will further allow us to better understand the mechanisms of selection in pig breeding.     

Population Genomic Analyses Based on 1 Million SNPs in Commercial Egg Layers

Identifying signatures of selection can provide valuable insight about the genes or genomic regions that are or have been under selective pressure, which can lead to a better understanding of genotype-phenotype relationships. A common strategy for selection signature detection is to compare samples from several populations and search for genomic regions with outstanding genetic differentiation. Wright''s fixation index, F_ST, is a useful index for evaluation of genetic differentiation between populations. The aim of this study was to detect selective signatures between different chicken groups based on SNP-wise F_ST calculation. A total of 96 individuals of three commercial layer breeds and 14 non-commercial fancy breeds were genotyped with three different 600K SNP-chips. After filtering a total of 1 million SNPs were available for F_ST calculation. Averages of F_ST values were calculated for overlapping windows. Comparisons of these were then conducted between commercial egg layers and non-commercial fancy breeds, as well as between white egg layers and brown egg layers. Comparing non-commercial and commercial breeds resulted in the detection of 630 selective signatures, while 656 selective signatures were detected in the comparison between the commercial egg-layer breeds. Annotation of selection signature regions revealed various genes corresponding to productions traits, for which layer breeds were selected. Among them were NCOA1, SREBF2 and RALGAPA1 associated with reproductive traits, broodiness and egg production. Furthermore, several of the detected genes were associated with growth and carcass traits, including POMC, PRKAB2, SPP1, IGF2, CAPN1, TGFb2 and IGFBP2. Our approach demonstrates that including different populations with a specific breeding history can provide a unique opportunity for a better understanding of farm animal selection.     

Evaluation of artificial selection in Standard Poodles using whole-genome sequencing

Identifying regions of artificial selection within dog breeds may provide insights into genetic variation that underlies breed-specific traits or diseases—particularly if these traits or disease predispositions are fixed within a breed. In this study, we searched for runs of homozygosity (ROH) and calculated the d _i statistic (which is based upon F _ST) to identify regions of artificial selection in Standard Poodles using high-coverage, whole-genome sequencing data of 15 Standard Poodles and 49 dogs across seven other breeds. We identified consensus ROH regions ≥1 Mb in length and common to at least ten Standard Poodles covering 0.6 % of the genome, and d _i regions that most distinguish Standard Poodles from other breeds covering 3.7 % of the genome. Within these regions, we identified enriched gene pathways related to olfaction, digestion, and taste, as well as pathways related to adrenal hormone biosynthesis, T cell function, and protein ubiquitination that could contribute to the pathogenesis of some Poodle-prevalent autoimmune diseases. We also validated variants related to hair coat and skull morphology that have previously been identified as being under selective pressure in Poodles, and flagged additional polymorphisms in genes such as ITGA2B, CBX4, and TNXB that may represent strong candidates for other common Poodle disorders.     

Genome‐wide assessment of diversity and differentiation between original and modern Brown cattle populations

Identifying genomic regions involved in the differences between breeds can provide information on genes that are under the influence of both artificial and natural selection. The aim of this study was to assess the genetic diversity and differentiation among four different Brown cattle populations (two original vs. two modern populations) and to characterize the distribution of runs of homozygosity (ROH) islands using the Illumina Bovine SNP50 BeadChip genotyping data. After quality control, 34 735 SNPs and 106 animals were retained for the analyses. Larger heterogeneity was highlighted for the original populations. Patterns of genetic differentiation, multidimensional scaling, and the neighboring joining tree distinguished the modern from the original populations. The F_ST‐outlier identified several genes putatively involved in the genetic differentiation between the two groups, such as stature and growth, behavior, and adaptability to local environments. The ROH islands within both the original and the modern populations overlapped with QTL associated with relevant traits. In modern Brown (Brown Swiss and Italian Brown), ROH islands harbored candidate genes associated with milk production traits, in evident agreement with the artificial selection conducted to improve this trait in these populations. In original Brown (Original Braunvieh and Braunvieh), we identified candidate genes related with fat deposition, confirming that breeding strategies for the original Brown populations aimed to produce dual‐purpose animals. Our study highlighted the presence of several genomic regions that vary between Brown populations, in line with their different breeding histories.     

Identifying candidate positive selection genes in Korean imported pig breeds

Domestication and artificial selection have modified the genome landscape of the pig. The identification of selection signatures in the genome can help to elucidate the selection mechanisms and uncover the causal genes related to the phenotypic variations between domestic pig breeds. We scanned the genomes of Korean imported pig breeds against native breeds using Z-transformed Fst (ZF_ST) and Heterozygosity (ZH_p) statistics to search for the signatures of positive selection. We identified 411 (ZF_ST?=?175; ZH_p?=?256) putatively selected genes in commercial breeds. The gene regions identified were harboring those related to immunity, coat color, reproduction function and other traits. Several genes (e.g., PLSCR4, AGTR1 and CORIN) were related to reproduction traits such as fertility, ovulation rate, and uterine function. This study revealed genes which improve our understanding of the biological mechanisms of higher litter sizes, the phenotype of interest, in higher litter pig breeds.     

Genome-wide analyses reveal population structure and identify candidate genes associated with tail fatness in local sheep from a semi-arid area

Under a climate change perspective, the genetic make-up of local livestock breeds showing adaptive traits should be explored and preserved as a priority. We used genotype data from the ovine 50 k Illumina BeadChip for assessing breed autozygosity based on runs of homozygosity (ROH) and fine-scale genetic structure and for detecting genomic regions under selection in 63 Tunisian sheep samples. The average genomic inbreeding coefficients based on ROH were estimated at 0.017, 0.021, and 0.024 for Barbarine (BAR, n = 26), Noire de Thibar (NDT, n = 23), and Queue fine de l'Ouest (QFO, n = 14) breeds, respectively. The genomic relationships among individuals based on identity by state (IBS) distance matrix highlighted a recent introgression of QFO into the BAR and a genetic differentiation of NDT samples, possibly explained by past introgression of European gene pools. Genome-wide scan for ROH across breeds and within the BAR sample set identified an outstanding signal on chromosome 13 (46.58–49.61 Mbp). These results were confirmed using F_ST index, differentiating fat vs. thin-tailed individuals. Candidate genes under selection pressure (CDS2, PROKR1, and BMP2) were associated to lipid storage and probably preferentially selected in fat-tailed BAR animals. Our findings suggest paying more attention to preserve the genetic integrity and adaptive alleles of local sheep breeds.     

Genetic structure and admixture in sheep from terminal breeds in the United States

Selection for performance in diverse production settings has resulted in variation across sheep breeds worldwide. Although sheep are an important species to the United States, the current genetic relationship among many terminal sire breeds is not well characterized. Suffolk, Hampshire, Shropshire and Oxford (terminal) and Rambouillet (dual purpose) sheep (n = 248) sampled from different flocks were genotyped using the Applied Biosystems Axiom Ovine Genotyping Array (50K), and additional Shropshire sheep (n = 26) using the Illumina Ovine SNP50 BeadChip. Relationships were investigated by calculating observed heterozygosity, inbreeding coefficients, eigenvalues, pairwise Wright’s F_ST estimates and an identity by state matrix. The mean observed heterozygosity for each breed ranged from 0.30 to 0.35 and was consistent with data reported in other US and Australian sheep. Suffolk from two different regions of the United States (Midwest and West) clustered separately in eigenvalue plots and the rectangular cladogram. Further, divergence was detected between Suffolk from different regions with Wright’s F_ST estimate. Shropshire animals showed the greatest divergence from other terminal breeds in this study. Admixture between breeds was examined using admixture , and based on cross-validation estimates, the best fit number of populations (clusters) was K = 6. The greatest admixture was observed within Hampshire, Suffolk, and Shropshire breeds. When plotting eigenvalues, US terminal breeds clustered separately in comparison with sheep from other locations of the world. Understanding the genetic relationships between terminal sire breeds in sheep will inform us about the potential applicability of markers derived in one breed to other breeds based on relatedness.     

EFBAT: exact family-based association tests

Background

Previous studies have reported frequent stretches of homozygosity in human subjects but have failed to clarify whether these are due to cytogenetic abnormalities or to autozygosity.

Methods

Trios which had been typed for closely spaced SNPs spanning the genome were studied. Stretches of extended homozygosity were identified in the child members, as were occasions on which the child had been genotyped as not inheriting one parental allele. The number of times such transmission errors occurred within regions of extended homozygosity was compared with the chance expectation.

Results

Transmission errors occurred more rarely in regions of extended homozygosity than would be expected by chance.

Discussion

Regions of extended homozygosity are not generally due to cytogenetic abnormalities such as uniparental isodisomy. They reflect the Mendelian inheritance of haplotypes from a common ancestor. This may have implications for mapping disease genes.     

Refinement of primate copy number variation hotspots identifies candidate genomic regions evolving under positive selection

Background

Copy number variants (CNVs), defined as losses and gains of segments of genomic DNA, are a major source of genomic variation.

Results

In this study, we identified over 2,000 human CNVs that overlap with orthologous chimpanzee or orthologous macaque CNVs. Of these, 170 CNVs overlap with both chimpanzee and macaque CNVs, and these were collapsed into 34 hotspot regions of CNV formation. Many of these hotspot regions of CNV formation are functionally relevant, with a bias toward genes involved in immune function, some of which were previously shown to evolve under balancing selection in humans. The genes in these primate CNV formation hotspots have significant differential expression levels between species and show evidence for positive selection, indicating that they have evolved under species-specific, directional selection.

Conclusions

These hotspots of primate CNV formation provide a novel perspective on divergence and selective pressures acting on these genomic regions.