Genetic variation analysis within and among six varieties of common carp (Cyprinus carpio L.) in China using microsatellite markers

Five microsatellites were used to study the genetic diversity and genetic structure of one wild and five domestic varieties of common carp in China (the Yangtze River wild common carp, Xingguo red carp, purse red carp, Qingtian carp, Russian scattered scaled mirror carp and Japanese decorative carp). All loci in this study showed marked polymorphism with the number of alleles from 4 to 13. Domestic varieties (except Xingguo red carp) showed less genetic diversity than the Yangtze River wild common carp in terms of allelic diversity. Population differentiation was assessed and each combination of populations displayed significant differentiation (p < 0.05) with the exception of that between the Yangtze River wild common carp and Xingguo red carp. Genetic distance analysis (Nei's standard genetic distance and pairwise F(st) distance) showed that the largest distance was between Russian scattered scaled mirror carp and the Yangtze River wild common carp and the smallest distance was between the Yangtze River wild common carp and Xingguo red carp. However, among six populations Japanese decorative carp displayed the highest level of variability in terms of heterozygosity.     

Genetic Variation Analysis within and among Six Varieties of Common Carp (Cyprinus carpio L.) in China Using Microsatellite Markers

Five microsatellites were used to study the genetic diversity and genetic structure of one wild and five domestic varieties of common carp in China (the Yangtze River wild common carp, Xingguo red carp, purse red carp, Qingtian carp, Russian scattered scaled mirror carp and Japanese decorative carp). All loci in this study showed marked polymorphism with the number of alleles ranging from 4 to 13. Domestic varieties (except Xingguo red carp) showed less genetic diversity than the Yangtze River wild common carp in terms of allelic diversity. Population differentiation was assessed and each combination of populations displayed significant differentiation (P < 0.05) with the exception of that between the Yangtze River wild common carp and Xingguo red carp. Genetic distance analysis (Nei's standard genetic distance and pairwise F _st distance) showed that the largest distance was between Russian scattered scaled mirror carp and the Yangtze River wild common carp and the smallest distance was between the Yangtze River wild common carp and Xingguo red carp. However, among six populations Japanese decorative carp displayed the highest level of variability in terms of heterozygosity.     

Molecular phylogeny of three subspecies of common carp Cyprinus carpio, based on sequence analysis of cytochrome b and control region of mtDNA

The complete cytochrome b and the control region of mtDNA (about 2070 bp in total) of 10 strains belonging to three subspecies of the common carp, including three wild subspecies (the Yangtze River wild common carp – Cyprinus carpio haematopterus , Yuanjiang River wild common carp – Cyprinus carpio rubrofuscus and Volga River wild common carp – Cyprinus carpio carpio ) and seven domestic strains (Xingguo red carp, Russian scattered scaled mirror carp, Qingtian carp, Japanese Koi carp, purse red carp, Big-belly carp, German mirror carp) were sequenced. Phylogenetic analysis indicated that the 10 strains form three distinct clades, corresponding to C. c. haematopterus , C. c. rubrofuscus and C. c. carpio respectively. Purse red carp, an endemic domestic strain in Jiangxi province of China, showed a higher evolution rate in comparison with the other strains of C. c. haematopterus , most probably because of intensive selection and a long history of domestication. Base variation ratios among the three subspecies varied from 0.78% (between C. c. haematopterus and C. c. rubrofuscus ) to 1.47%(between C. c. carpio and C. c. rubrofuscus ). The topography of the phylogenetic tree and the geographic distribution of three subspecies closely resemble each other. The divergence time between C. c. carpio and the other two subspecies was estimated to be about 0.9 Myr and about 0.5 Myr between C. c. haematopterus and C. c. rubrofuscus . Based on phylogenetic analysis, C. c. rubrofuscus might have diverged from C. c. haematopterus .     

Determination of the surface area of common carp,Cyprinus carpio L.

A wrap method adaptation combined with AutoCAD2005 and Scion Image for Windows were used to determine the surface area of a fish. Compared with the corresponding r² and F of many models, the most accurate formula: S = 752.15W^0.675 (r² = 0.999, F = 18362.94, P < 0.0001) for estimating the surface area of common carp was obtained. Similarly, the fin formula: S = 1834.12W^0.708 (r² = 0.992, F = 2690.47, P < 0.0001) was also obtained for the same purpose. It was proven that these two formulae gave good estimates of surface and fin areas of four strains of common carp: Yellow‐river carp, fancy carp, mirror carp and Xingguo red carp.     

Genome-Scale Association Study of Abnormal Scale Pattern in Yellow River Carp Identified Previously Known Causative Gene in European Mirror Carp

Common carp (Cyprinus carpio) is one of the most widely studied fish species due to its great economic value and strong environmental adaptability. Scattered scale, a typical phenotype of the mirror carp that is derived from Europe, has never been observed in the Yellow River carp previously. We recently identified approximately one fourth of the F1 progenies displaying scattered scale in a full-sib Yellow River carp family in our breeding program, despite both parents that showed wild type with normal scale patterns. This family provides us unique materials to investigate the genetic basis underlying the abnormal scale mutant in Yellow River carp population. Genome-wide association study (GWAS) and association mapping were performed based on genome-wide single nucleotide polymorphisms (SNP) genotyped with common carp 250 K SNP genotyping array in 82 samples of the Yellow River carp family. We identified a 1.4 Mb genome region that was significantly associated with abnormal scattered scale patterns. We further identified a deletion mutation in fibroblast growth factor receptor 1 a1 (fgfr1a1) gene within this genome region. Amplification and sequencing analysis of this gene revealed a 311-bp deletion in intron 10 and exon 11, which proved that fgfr1a1 could be the causal gene responsible for abnormal scattered scale in the Yellow River carp family. Since similar fragment mutation with 306-bp and 310-bp deletions had been previously reported as causal mutation of scattered scale patterns in the mirror carp, we speculate that either the deletion mutation was introduced from Europe-derived mirror carp or the deletion independently occurred in the mutation hotspot in fgfr1a1 gene. The results provided insights into the genetic basis of scale pattern mutant in Yellow River carp population, which would help us to eliminate the recessive allele of the abnormal scale patterns in Yellow River carp population by molecular marker-assisted breeding.     

Genetic divergence between Cyprinus carpio carpio and Cyprinus carpio haematopterus as assessed by mitochondrial DNA analysis,with emphasis on origin of European domestic carp

Although common carp is the major fish species in Asian and European aquaculture and many domestic varieties have occurred, there is a controversy about the origination of European domestic common carp. Some scientists affirmed that the ancestor of European domestic common carp was Danube River wild common carp, but others considered it might be Asian common carp. For elucidating origination of European domestic common carp, we chose two representative European domestic common carp strains (German mirror carp and Russian scattered scaled mirror carp) and one wild common carp strain of Cyprinus carpio carpio subspecies (Volga River wild common carp) and two Asian common carp strains, the Yangtze River wild common carp (Cyprinus carpio haematopterus) and traditionally domestic Xingguo red common carp, as experimental materials. ND5–ND6 and D-loop segments of mitochondrial DNA were amplified by polymerase chain reaction and analyzed through restriction fragment length polymorphism (RFLP) and sequencing respectively. The results revealed that HaeIII and DdeI digestion patterns of ND5–ND6 segment and sequences of control region were different between European subspecies C. carpio carpio and Asian subspecies C. carpio haematopterus. Phylogenetic analysis showed that German mirror carp and Russian scattered scaled mirror carp belonged to two subspecies, C. carpio carpio and C. carpio haematopterus, respectively. Therefore, there were different ancestors for domestic carp in Europe: German mirror carp was domesticated from European subspecies C. carpio carpio and Russian scattered scaled mirror carp originated from Asian subspecies C. carpio haematopterus.     

Non-synonymous mutations mapped to chromosome X associated with andrological and growth traits in beef cattle

Background

Previous genome-wide association analyses identified QTL regions in the X chromosome for percentage of normal sperm and scrotal circumference in Brahman and Tropical Composite cattle. These traits are important to be studied because they are indicators of male fertility and are correlated with female sexual precocity and reproductive longevity. The aim was to investigate candidate genes in these regions and to identify putative causative mutations that influence these traits. In addition, we tested the identified mutations for female fertility and growth traits.

Results

Using a combination of bioinformatics and molecular assay technology, twelve non-synonymous SNPs in eleven genes were genotyped in a cattle population. Three and nine SNPs explained more than 1% of the additive genetic variance for percentage of normal sperm and scrotal circumference, respectively. The SNPs that had a major influence in percentage of normal sperm were mapped to LOC100138021 and TAF7L genes; and in TEX11 and AR genes for scrotal circumference. One SNP in TEX11 was explained ~13% of the additive genetic variance for scrotal circumference at 12 months. The tested SNP were also associated with weight measurements, but not with female fertility traits.

Conclusions

The strong association of SNPs located in X chromosome genes with male fertility traits validates the QTL. The implicated genes became good candidates to be used for genetic evaluation, without detrimentally influencing female fertility traits.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1595-0) contains supplementary material, which is available to authorized users.     

Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology

Background

The dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design a high-density SNP genotyping assay.

Methodology/Principal Findings

A total of 19 reduced representation libraries derived from four swine breeds (Duroc, Landrace, Large White, Pietrain) and a Wild Boar population and three restriction enzymes (AluI, HaeIII and MspI) were sequenced using Illumina''s Genome Analyzer (GA). The SNP discovery effort resulted in the de novo identification of over 372K SNPs. More than 549K SNPs were used to design the Illumina Porcine 60K+SNP iSelect Beadchip, now commercially available as the PorcineSNP60. A total of 64,232 SNPs were included on the Beadchip. Results from genotyping the 158 individuals used for sequencing showed a high overall SNP call rate (97.5%). Of the 62,621 loci that could be reliably scored, 58,994 were polymorphic yielding a SNP conversion success rate of 94%. The average minor allele frequency (MAF) for all scorable SNPs was 0.274.

Conclusions/Significance

Overall, the results of this study indicate the utility of using next generation sequencing technologies to identify large numbers of reliable SNPs. In addition, the validation of the PorcineSNP60 Beadchip demonstrated that the assay is an excellent tool that will likely be used in a variety of future studies in pigs.     

First Genome-Wide Association Study on Anxiety-Related Behaviours in Childhood

Background

Twin studies have shown that anxiety in a general population sample of children involves both domain-general and trait-specific genetic effects. For this reason, in an attempt to identify genes responsible for these effects, we investigated domain-general and trait-specific genetic associations in the first genome-wide association (GWA) study on anxiety-related behaviours (ARBs) in childhood.

Methods

The sample included 2810 7-year-olds drawn from the Twins Early Development Study (TEDS) with data available for parent-rated anxiety and genome-wide DNA markers. The measure was the Anxiety-Related Behaviours Questionnaire (ARBQ), which assesses four anxiety traits and also yields a general anxiety composite. Affymetrix GeneChip 6.0 DNA arrays were used to genotype nearly 700,000 single-nucleotide polymorphisms (SNPs), and IMPUTE v2 was used to impute more than 1 million SNPs. Several GWA associations from this discovery sample were followed up in another TEDS sample of 4804 children. In addition, Genome-wide Complex Trait Analysis (GCTA) was used on the discovery sample, to estimate the total amount of variance in ARBs that can be accounted for by SNPs on the array.

Results

No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome (p<5×10⁻⁸). Attempts to replicate the top associations did not yield significant results. In contrast to the substantial twin study estimates of heritability which ranged from 0.50 (0.03) to 0.61 (0.01), the GCTA estimates of phenotypic variance accounted for by the SNPs were much lower 0.01 (0.11) to 0.19 (0.12).

Conclusions

Taken together, these GWAS and GCTA results suggest that anxiety – similar to height, weight and intelligence − is affected by many genetic variants of small effect, but unlike these other prototypical polygenic traits, genetic influence on anxiety is not well tagged by common SNPs.     

Genome wide CNV analysis reveals additional variants associated with milk production traits in Holsteins

Background

Milk production is an economically important sector of global agriculture. Much attention has been paid to the identification of quantitative trait loci (QTL) associated with milk, fat, and protein yield and the genetic and molecular mechanisms underlying them. Copy number variation (CNV) is an emerging class of variants which may be associated with complex traits.

Results

In this study, we performed a genome-wide association between CNVs and milk production traits in 26,362 Holstein bulls and cows. A total of 99 candidate CNVs were identified using Illumina BovineSNP50 array data, and association tests for each production trait were performed using a linear regression analysis with PCA correlation. A total of 34 CNVs on 22 chromosomes were significantly associated with at least one milk production trait after false discovery rate (FDR) correction. Some of those CNVs were located within or near known QTL for milk production traits. We further investigated the relationship between associated CNVs with neighboring SNPs. For all 82 combinations of traits and CNVs (less than 400 kb in length), we found 17 cases where CNVs directly overlapped with tag SNPs and 40 cases where CNVs were adjacent to tag SNPs. In 5 cases, CNVs located were in strong linkage disequilibrium with tag SNPs, either within or adjacent to the same haplotype block. There were an additional 20 cases where CNVs did not have a significant association with SNPs, suggesting that the effects of those CNVs were probably not captured by tag SNPs.

Conclusion

We conclude that combining CNV with SNP analyses reveals more genetic variations underlying milk production traits than those revealed by SNPs alone.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-683) contains supplementary material, which is available to authorized users.     

Common Genetic Variation in the Human CTF1 Locus,Encoding Cardiotrophin-1, Determines Insulin Sensitivity

Aims/Hypothesis

Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs) in the CTF1 locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans.

Methods

We genotyped 1,771 German subjects for three CTF1 tagging SNPs (rs1046276, rs1458201, and rs8046707). The subjects were metabolically characterized by an oral glucose tolerance test. Subgroups underwent magnetic resonance (MR) imaging/spectroscopy and hyperinsulinaemic-euglycaemic clamps.

Results

After appropriate adjustment, the minor allele of CTF1 SNP rs8046707 was significantly associated with decreased in vivo measures of insulin sensitivity. The other tested SNPs were not associated with OGTT-derived sensitivity parameters, nor did the three tested SNPs show any association with OGTT-derived parameters of insulin release. In the MR subgroup, SNP rs8046707 was nominally associated with lower visceral adipose tissue. Furthermore, the SNP rs1458201 showed a nominal association with increased VLDL levels.

Conclusions

In conclusion, this study, even though preliminary and awaiting further confirmation by independent replication, provides first evidence that common genetic variation in CTF1 could contribute to insulin sensitivity in humans. Our SNP data indicate an insulin-desensitizing effect of cardiotrophin-1 and underline that cardiotrophin-1 represents an interesting target to influence insulin sensitivity.     

Genome-wide association analysis of seedling root development in maize (Zea mays L.)

Background

Plants rely on the root system for anchorage to the ground and the acquisition and absorption of nutrients critical to sustaining productivity. A genome wide association analysis enables one to analyze allelic diversity of complex traits and identify superior alleles. 384 inbred lines from the Ames panel were genotyped with 681,257 single nucleotide polymorphism markers using Genotyping-by-Sequencing technology and 22 seedling root architecture traits were phenotyped.

Results

Utilizing both a general linear model and mixed linear model, a GWAS study was conducted identifying 268 marker trait associations (p ≤ 5.3×10^-7). Analysis of significant SNP markers for multiple traits showed that several were located within gene models with some SNP markers localized within regions of previously identified root quantitative trait loci. Gene model GRMZM2G153722 located on chromosome 4 contained nine significant markers. This predicted gene is expressed in roots and shoots.

Conclusion

This study identifies putatively associated SNP markers associated with root traits at the seedling stage. Some SNPs were located within or near (<1 kb) gene models. These gene models identify possible candidate genes involved in root development at the seedling stage. These and respective linked or functional markers could be targets for breeders for marker assisted selection of seedling root traits.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1226-9) contains supplementary material, which is available to authorized users.     

Genome-wide association study identifies Loci for body composition and structural soundness traits in pigs

Background

The recent completion of the swine genome sequencing project and development of a high density porcine SNP array has made genome-wide association (GWA) studies feasible in pigs.

Methodology/Principal Findings

Using Illumina''s PorcineSNP60 BeadChip, we performed a pilot GWA study in 820 commercial female pigs phenotyped for backfat, loin muscle area, body conformation in addition to feet and leg (FL) structural soundness traits. A total of 51,385 SNPs were jointly fitted using Bayesian techniques as random effects in a mixture model that assumed a known large proportion (99.5%) of SNPs had zero effect. SNP annotations were implemented through the Sus scrofa Build 9 available from pig Ensembl. We discovered a number of candidate chromosomal regions, and some of them corresponded to QTL regions previously reported. We not only have identified some well-known candidate genes for the traits of interest, such as MC4R (for backfat) and IGF2 (for loin muscle area), but also obtained novel promising genes, including CHCHD3 (for backfat), BMP2 (for loin muscle area, body size and several FL structure traits), and some HOXA family genes (for overall leg action). The candidate regions responsible for body conformation and FL structure soundness did not overlap greatly which implied that these traits were controlled by different genes. Functional clustering analyses classified the genes into categories related to bone and cartilage development, muscle growth and development or the insulin pathway suggesting the traits are regulated by common pathways or gene networks that exert roles at different spatial and temporal stages.

Conclusions/Significance

This study is one of the earliest GWA reports on important quantitative traits in pigs, and the findings will contribute to the further biological function analysis of the identified candidate genes and potential utilization of them in marker assisted selection.     

Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight

Background

Body weight (BW) is an important trait for meat production in sheep. Although over the past few years, numerous quantitative trait loci (QTL) have been detected for production traits in cattle, few QTL studies have been reported for sheep, with even fewer on meat production traits. Our objective was to perform a genome-wide association study (GWAS) with the medium-density Illumina Ovine SNP50 BeadChip to identify genomic regions and corresponding haplotypes associated with BW in Australian Merino sheep.

Methods

A total of 1781 Australian Merino sheep were genotyped using the medium-density Illumina Ovine SNP50 BeadChip. Among the 53 862 single nucleotide polymorphisms (SNPs) on this array, 48 640 were used to perform a GWAS using a linear mixed model approach. Genotypes were phased with hsphase; to estimate SNP haplotype effects, linkage disequilibrium blocks were identified in the detected QTL region.

Results

Thirty-nine SNPs were associated with BW at a Bonferroni-corrected genome-wide significance threshold of 1 %. One region on sheep (Ovis aries) chromosome 6 (OAR6) between 36.15 and 38.56 Mb, included 13 significant SNPs that were associated with BW; the most significant SNP was OAR6_41936490.1 (P = 2.37 × 10⁻¹⁶) at 37.69 Mb with an allele substitution effect of 2.12 kg, which corresponds to 0.248 phenotypic standard deviations for BW. The region that surrounds this association signal on OAR6 contains three genes: leucine aminopeptidase 3 (LAP3), which is involved in the processing of the oxytocin precursor; NCAPG non-SMC condensin I complex, subunit G (NCAPG), which is associated with foetal growth and carcass size in cattle; and ligand dependent nuclear receptor corepressor-like (LCORL), which is associated with height in humans and cattle.

Conclusions

The GWAS analysis detected 39 SNPs associated with BW in sheep and a major QTL region was identified on OAR6. In several other mammalian species, regions that are syntenic with this region have been found to be associated with body size traits, which may reflect that the underlying biological mechanisms share a common ancestry. These findings should facilitate the discovery of causative variants for BW and contribute to marker-assisted selection.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0142-4) contains supplementary material, which is available to authorized users.     

Genome-wide association analyses for meat quality traits in Chinese Erhualian pigs and a Western Duroc?×?(Landrace × Yorkshire) commercial population

Background

Understanding the genetic mechanisms that underlie meat quality traits is essential to improve pork quality. To date, most quantitative trait loci (QTL) analyses have been performed on F₂ crosses between outbred pig strains and have led to the identification of numerous QTL. However, because linkage disequilibrium is high in such crosses, QTL mapping precision is unsatisfactory and only a few QTL have been found to segregate within outbred strains, which limits their use to improve animal performance. To detect QTL in outbred pig populations of Chinese and Western origins, we performed genome-wide association studies (GWAS) for meat quality traits in Chinese purebred Erhualian pigs and a Western Duroc × (Landrace × Yorkshire) (DLY) commercial population.

Methods

Three hundred and thirty six Chinese Erhualian and 610 DLY pigs were genotyped using the Illumina PorcineSNP60K Beadchip and evaluated for 20 meat quality traits. After quality control, 35 985 and 56 216 single nucleotide polymorphisms (SNPs) were available for the Chinese Erhualian and DLY datasets, respectively, and were used to perform two separate GWAS. We also performed a meta-analysis that combined P-values and effects of 29 516 SNPs that were common to Erhualian, DLY, F₂ and Sutai pig populations.

Results

We detected 28 and nine suggestive SNPs that surpassed the significance level for meat quality in Erhualian and DLY pigs, respectively. Among these SNPs, ss131261254 on pig chromosome 4 (SSC4) was the most significant (P = 7.97E-09) and was associated with drip loss in Erhualian pigs. Our results suggested that at least two QTL on SSC12 and on SSC15 may have pleiotropic effects on several related traits. All the QTL that were detected by GWAS were population-specific, including 12 novel regions. However, the meta-analysis revealed seven novel QTL for meat characteristics, which suggests the existence of common underlying variants that may differ in frequency across populations. These QTL regions contain several relevant candidate genes.

Conclusions

These findings provide valuable insights into the molecular basis of convergent evolution of meat quality traits in Chinese and Western breeds that show divergent phenotypes. They may contribute to genetic improvement of purebreds for crossbred performance.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0120-x) contains supplementary material, which is available to authorized users.     

Detection of quantitative trait loci in Bos indicus and Bos taurus cattle using genome-wide association studies

Background

The apparent effect of a single nucleotide polymorphism (SNP) on phenotype depends on the linkage disequilibrium (LD) between the SNP and a quantitative trait locus (QTL). However, the phase of LD between a SNP and a QTL may differ between Bos indicus and Bos taurus because they diverged at least one hundred thousand years ago. Here, we test the hypothesis that the apparent effect of a SNP on a quantitative trait depends on whether the SNP allele is inherited from a Bos taurus or Bos indicus ancestor.

Methods

Phenotype data on one or more traits and SNP genotype data for 10 181 cattle from Bos taurus, Bos indicus and composite breeds were used. All animals had genotypes for 729 068 SNPs (real or imputed). Chromosome segments were classified as originating from B. indicus or B. taurus on the basis of the haplotype of SNP alleles they contained. Consequently, SNP alleles were classified according to their sub-species origin. Three models were used for the association study: (1) conventional GWAS (genome-wide association study), fitting a single SNP effect regardless of subspecies origin, (2) interaction GWAS, fitting an interaction between SNP and subspecies-origin, and (3) best variable GWAS, fitting the most significant combination of SNP and sub-species origin.

Results

Fitting an interaction between SNP and subspecies origin resulted in more significant SNPs (i.e. more power) than a conventional GWAS. Thus, the effect of a SNP depends on the subspecies that the allele originates from. Also, most QTL segregated in only one subspecies, suggesting that many mutations that affect the traits studied occurred after divergence of the subspecies or the mutation became fixed or was lost in one of the subspecies.

Conclusions

The results imply that GWAS and genomic selection could gain power by distinguishing SNP alleles based on their subspecies origin, and that only few QTL segregate in both B. indicus and B. taurus cattle. Thus, the QTL that segregate in current populations likely resulted from mutations that occurred in one of the subspecies and can have both positive and negative effects on the traits. There was no evidence that selection has increased the frequency of alleles that increase body weight.     

Gene-centric characteristics of genome-wide association studies

Background

The high-throughput genotyping chips have contributed greatly to genome-wide association (GWA) studies to identify novel disease susceptibility single nucleotide polymorphisms (SNPs). The high-density chips are designed using two different SNP selection approaches, the direct gene-centric approach, and the indirect quasi-random SNPs or linkage disequilibrium (LD)-based tagSNPs approaches. Although all these approaches can provide high genome coverage and ascertain variants in genes, it is not clear to which extent these approaches could capture the common genic variants. It is also important to characterize and compare the differences between these approaches.

Methodology/Principal Findings

In our study, by using both the Phase II HapMap data and the disease variants extracted from OMIM, a gene-centric evaluation was first performed to evaluate the ability of the approaches in capturing the disease variants in Caucasian population. Then the distribution patterns of SNPs were also characterized in genic regions, evolutionarily conserved introns and nongenic regions, ontologies and pathways. The results show that, no mater which SNP selection approach is used, the current high-density SNP chips provide very high coverage in genic regions and can capture most of known common disease variants under HapMap frame. The results also show that the differences between the direct and the indirect approaches are relatively small. Both have similar SNP distribution patterns in these gene-centric characteristics.

Conclusions/Significance

This study suggests that the indirect approaches not only have the advantage of high coverage but also are useful for studies focusing on various functional SNPs either in genes or in the conserved regions that the direct approach supports. The study and the annotation of characteristics will be helpful for designing and analyzing GWA studies that aim to identify genetic risk factors involved in common diseases, especially variants in genes and conserved regions.