Estimates Of Inbreeding Coefficients Research Articles

A comparison of marker-based estimators of inbreeding and inbreeding depression

BackgroundThe availability of genome-wide marker data allows estimation of inbreeding coefficients (F, the probability of identity-by-descent, IBD) and, in turn, estimation of the rate of inbreeding depression (ΔID). We investigated, by computer simulations, the accuracy of the most popular estimators of inbreeding based on molecular markers when computing F and ΔID in populations under random mating, equalization of parental contributions, and artificially selected populations. We assessed estimators described by Li and Horvitz (FLH1 and FLH2), VanRaden (FVR1 and FVR2), Yang and colleagues (FYA1 and FYA2), marker homozygosity (FHOM), runs of homozygosity (FROH) and estimates based on pedigree (FPED) in comparison with estimates obtained from IBD measures (FIBD).ResultsIf the allele frequencies of a base population taken as a reference for the computation of inbreeding are known, all estimators based on marker allele frequencies are highly correlated with FIBD and provide accurate estimates of the mean ΔID. If base population allele frequencies are unknown and current frequencies are used in the estimations, the largest correlation with FIBD is generally obtained by FLH1 and the best estimator of ΔID is FYA2. The estimators FVR2 and FLH2 have the poorest performance in most scenarios. The assumption that base population allele frequencies are equal to 0.5 results in very biased estimates of the average inbreeding coefficient but they are highly correlated with FIBD and give relatively good estimates of ΔID. Estimates obtained directly from marker homozygosity (FHOM) substantially overestimated ΔID. Estimates based on runs of homozygosity (FROH) provide accurate estimates of inbreeding and ΔID. Finally, estimates based on pedigree (FPED) show a lower correlation with FIBD than molecular estimators but provide rather accurate estimates of ΔID. An analysis of data from a pig population supports the main findings of the simulations.ConclusionsWhen base population allele frequencies are known, all marker-allele frequency-based estimators of inbreeding coefficients generally show a high correlation with FIBD and provide good estimates of ΔID. When base population allele frequencies are unknown, FLH1 is the marker frequency-based estimator that is most correlated with FIBD, and FYA2 provides the most accurate estimates of ΔID. Estimates from FROH are also very precise in most scenarios. The estimators FVR2 and FLH2 have the poorest performances.

Evolutionary dynamics inform management interventions of a hanging garden obligate, Carex specuicola

Uncovering the historical and contemporary processes shaping rare species with complex distributions is of growing importance due to threats such as habitat destruction and climate change. Species restricted to specialized, patchy habitat may persist by virtue of life history characteristics facilitating ongoing gene flow and dispersal, but they could also reflect the remnants of formerly widespread, suitable habitat that existed during past climate regimes. If formerly widespread species did not rely upon traits facilitating high dispersibility to persist, contemporary populations could be at high risk of extirpation or extinction. Fortunately, genomic investigations provide an opportunity to illuminate such alternative scenarios while simultaneously offering guidance for future management interventions. Herein, we test the role of these mechanisms in shaping patterns of genomic diversity and differentiation across a highly restricted and rare ecosystem: desert hanging gardens. We focus on Carex specuicola (Cyperaceae), a hanging garden obligate narrowly distributed in the Four Corners region of the southwestern United States that is listed as Threatened under the United States Endangered Species Act. Population structure and diversity analyses reveal that hanging garden populations are shaped by strong genetic drift, but that individuals in gardens are occasionally more closely related to individuals at other gardens than to individuals within the same garden. Similarly, gardens separated by long geographic distances may contain individuals that are more closely related compared to individuals in gardens separated by short geographic distances. Demographic modeling supports historical gene flow between some contemporary garden pairs, which is corroborated by low estimates of inbreeding coefficients and recent divergence times. As such, multiple lines of evidence support dispersal and gene flow across C. specuicola populations at both small and large spatial scales, indicating that even if C. specuicola was formerly more widespread, it may be well suited to persist in hanging gardens so long as suitable habitat remains available. Analyses like those demonstrated herein may be broadly applicable for understanding the short- and long-term evolutionary processes influencing rare species, and especially those having complex distributions across heterogeneous landscapes.

Phenotypic trend, breeding value and heritability of biometric traits in Marwari horses

Analysis of phenotypic trend and estimation of inbreeding coefficient, breeding value and heritability of biometric traits was carried out for a total of 226 Marwari horses. The pedigree construct divided the entire population of 226 horses into 6 tiers spanning over a period of 30 years. The inbreeding coefficient of the herd was estimated to be 0.0017. The average height at withers, body length, heart girth and body weight of Marwari horses was 150.15±0.04 cm, 151.44±0.06 cm; 170.02±0.19 cm and 371.34±0.52 kg, respectively with non-significant effect of sex, tier and interaction of sex and tier. The Best Linear Unbiased Prediction (BLUP) estimate of breeding value for the height at withers (150.45 cm), body length (151.97 cm), heart girth (169.73 cm) and body weight (366.3 kg) for Marwari horses was -0.059 cm, -0.079 cm, 0.096 cm and 3.526 kg, respectively. The effect of sex and interaction of sex and tiers was non-significant but that of tier on the estimated breeding value for body weight was significant indicating that body weight received favour in breeding programme. The heritability of height at withers, body length, heart girth and body weight has been estimated to be 0.396±0.586, 0.370±0.777, 0.507±1.95 and 0.597±0.612, respectively. Negligible inbreeding and constant phenotype over decades indicated that the Marwari herd has been bred to maintain enough genetic variation and hence it can be the most reliable source of the stallions and mares for propagation and conservation of this legendry breed of horse which is getting diluted and declining at a faster rate.

Genome-Wide Assessment of Runs of Homozygosity and Estimates of Genomic Inbreeding in a Chinese Composite Pig Breed.

The primary purpose of the current study was to assess the genetic diversity, runs of homozygosity (ROH) and ROH islands in a Chinese composite pig and explore hotspot regions for traces of selection. First, we estimated the length, number, and frequency of ROH in 262 Xidu black pigs using the Porcine SNP50 BeadChip and compared the estimates of inbreeding coefficients, which were calculated based on ROHs (FROH) and homozygosity (FHOM). Our result shows that a total of 7,248 ROH exceeding 1Mb were detected in 262 pigs. In addition, Sus scrofa chromosome (SSC) 8 and SSC10, respectively, has the highest and lowest chromosome coverage by ROH. These results suggest that inbreeding estimation based on total ROH may be a useful method, especially for crossbreed or composite populations. We also calculated an inbreeding coefficient of 0.077 from the total ROH. Eight ROH islands were found in this study. These ROH islands harbored genes associated with fat deposition, muscular development, reproduction, ear shape, and adaptation, such as TRAF7, IGFBP7, XPO1, SLC26A8, PPARD, and OR1F1. These findings may help to understand the effects of environmental and artificial selection on the genome structure of composite pigs. Our results provide a basis for subsequent genomic selection (GS), and provides a reference for the hybrid utilization of other pig breeds.

Investigating inbreeding in the turkey (Meleagris gallopavo) genome

The detrimental effects of increased homozygosity due to inbreeding have prompted the development of methods to reduce inbreeding. The detection of runs of homozygosity (ROH), or contiguous stretches of homozygous marker genotypes, can be used to describe and quantify the level of inbreeding in an individual. The estimation of inbreeding coefficients can be calculated based on pedigree information, ROH, or the genomic relationship matrix. The aim of this study was to detect and describe ROH in the turkey genome and compare estimates of pedigree-based inbreeding coefficients (FPED) with genomic-based inbreeding coefficients estimated from ROH (FROH) and the genomic relationship matrix (FGRM). A total of 2,616,890 pedigree records were available. Of these records, 6,371 genotyped animals from three purebred turkey (Meleagris gallopavo) lines between 2013 and 2019 were available, and these were obtained using a dense single nucleotide polymorphism array (56,452 SNPs). The overall mean length of detected ROH was 2.87 ± 0.29 Mb with a mean number of 84.87 ± 8.79 ROH per animal. Short ROH with lengths of 1 to 2 Mb long were the most abundant throughout the genome. Mean ROH coverage differed greatly between chromosomes and lines. Considering inbreeding coefficient means across all lines, genomic derived inbreeding coefficients (FROH = 0.27; FGRM = 0.32) were higher than coefficients estimated from pedigree records (FPED = 0.14). Correlations between FROH and FPED, FROH and FGRM, and FPED and FGRM ranged between 0.19 to 0.31, 0.68 to 0.73, and 0.17 to 0.30, respectively. Additionally, correlations between FROH from different lengths and FPED substantially increased with ROH length from -0.06 to 0.33. Results of the current research, including the distribution of ROH throughout the genome and ROH-derived inbreeding estimates, can provide a more comprehensive description of inbreeding in the turkey genome. This knowledge can be used to evaluate genetic diversity, a requirement for genetic improvement, and develop methods to minimize inbreeding in turkey breeding programs.

Estimation of inbreeding and identification of regions under heavy selection based on runs of homozygosity in a Large White pig population

BackgroundRuns of homozygosity (ROHs) are homozygous segments of the genome where the two haplotypes inherited from the parents are identical. The current availability of genotypes for a very large number of single nucleotide polymorphisms (SNPs) is leading to more accurate characterization of ROHs in the whole genome. Here, we investigated the occurrence and distribution of ROHs in 3,692 Large White pigs and compared estimates of inbreeding coefficients calculated based on ROHs (FROH), homozygosity (FHOM), genomic relationship matrix (FGRM) and pedigree (FPED). Furthermore, we identified genomic regions with high ROH frequencies and annotated their candidate genes.ResultsIn total, 176,182 ROHs were identified from 3,569 animals, and all individuals displayed at least one ROH longer than 1 Mb. The ROHs identified were unevenly distributed on the autosomes. The highest and lowest coverages of Sus scrofa chromosomes (SSC) by ROH were on SSC14 and SSC13, respectively. The highest pairwise correlation among the different inbreeding coefficient estimates was 0.95 between FROH_total and FHOM, while the lowest was − 0.083 between FGRM and FPED. The correlations between FPED and FROH using four classes of ROH lengths ranged from 0.18 to 0.37 and increased with increasing ROH length, except for ROH > 10 Mb. Twelve ROH islands were located on four chromosomes (SSC1, 4, 6 and 14). These ROH islands harboured genes associated with reproduction, muscular development, fat deposition and adaptation, such as SIRT1, MYPN, SETDB1 and PSMD4.ConclusionFROH can be used to accurately assess individual inbreeding levels compared to other inbreeding coefficient estimators. In the absence of pedigree records, FROH can provide an alternative to inbreeding estimates. Our findings can be used not only to effectively increase the response to selection by appropriately managing the rate of inbreeding and minimizing the negative effects of inbreeding depression but also to help detect genomic regions with an effect on traits under selection.

A Genetic Investigation of Island Jersey Cattle, the Foundation of the Jersey Breed: Comparing Population Structure and Selection to Guernsey, Holstein, and United States Jersey Cattle.

For two centuries, Jersey cattle were exported globally, adapting to varying climates and production systems, yet the founding population remained genetically isolated on the Island of Jersey. The Island of Jersey formally allowed the importation of pure Jersey cattle in 2008. This study characterized the genetic variation of 49 popular bulls from the Island of Jersey born from 1964 to 2004 and compared them to 47 non-Island Jersey bulls and cows, primarily from the United States In addition, 21 Guernsey cattle derived from the Island of Guernsey and 71 Holstein cattle served as reference populations for genetic comparison. Cattle were genotyped on the Illumina BovineHD Beadchip producing 777,962 SNPs spanning the genome. Principal component analysis revealed population stratification within breed reflective of individual animal’s continental origin. When compared to Holstein and Guernsey, all Jersey clustered together by breed. The Jersey breed demonstrated increased inbreeding in comparison to Holstein or Guernsey with slightly higher estimates of inbreeding coefficients and identity-by-descent. The Island and United States Jersey have relatively similar, yet statistically different inbreeding estimates despite vastly different population sizes and gene flow. Signatures of selection within Island Jersey were identified using genome-wide homozygosity association and marker-based FST that provided population informative single-nucleotide polymorphism (SNPs). Biological significance of the homozygosity association results identified multiple genes on chromosomes 5, 24, and 27, involved in immune function and cellular processes. Overall, genomic variation was identified between the Island and non-Island Jersey cattle producing population informative SNPs and differing runs of homozygosity (ROH) over immune regulation and metabolic genes. Results on inbreeding measures and ROH may reflect varying effective population size or differential selection with grazing systems promoting natural selection for traits such as parasite resistance, whereas confinement systems demonstrate a more intensive artificial selection. More broadly, differences in breed formation, particularly between the two Channel Island breeds, likely contributed to the variation in ROH and inbreeding. This research provides a reference for the Jersey breed based on the genetic foundation of the Island cattle as compared to the intensively selected United States cattle, and identifies regions of the genome for future investigation of immune regulation and metabolic processes.

Inbreeding shapes the evolution of marine invertebrates.

Inbreeding is a potent evolutionary force shaping the distribution of genetic variation within and among populations of plants and animals. Yet, our understanding of the forces shaping the expression and evolution of nonrandom mating in general, and inbreeding in particular, remains remarkably incomplete. Most research on plant mating systems focuses on self‐fertilization and its consequences for automatic selection, inbreeding depression, purging, and reproductive assurance, whereas studies of animal mating systems have often assumed that inbreeding is rare, and that natural selection favors traits that promote outbreeding. Given that many sessile and sedentary marine invertebrates and marine macroalgae share key life history features with seed plants (e.g., low mobility, modular construction, and the release of gametes into the environment), their mating systems may be similar. Here, we show that published estimates of inbreeding coefficients (F IS) for sessile and sedentary marine organisms are similar and at least as high as noted in terrestrial seed plants. We also found that variation in F IS within invertebrates is related to the potential to self‐fertilize, disperse, and choose mates. The similarity of F IS for these organismal groups suggests that inbreeding could play a larger role in the evolution of sessile and sedentary marine organisms than is currently recognized. Specifically, associations between traits of marine invertebrates and F IS suggest that inbreeding could drive evolutionary transitions between hermaphroditism and separate sexes, direct development and multiphasic life cycles, and external and internal fertilization.

The simulation extrapolation technique meets ecology and evolution: A general and intuitive method to account for measurement error

Abstract Measurement error and other forms of uncertainty are commonplace in ecology and evolution, and may bias estimates of parameters of interest. Although a variety of approaches to obtain unbiased estimators are available, these usually require the formulation of an explicit (parametric) model for the error‐prone variable and a latent model for the unobserved (latent) error‐free variable. In practice, this is often difficult. We propose to generalize the simulation extrapolation (SIMEX) technique, a heuristic approach to correct for measurement error, to situations where it is difficult to explicitly formulate an error model or latent model for a variable of interest. We illustrate the idea with the example of error in pedigrees. Pedigree error causes error in estimates of inbreeding coefficients and the relatedness matrix, thus biasing estimates of inbreeding depression or heritability. Instead of formulating error models for inbreeding coefficients or the relatedness matrix, we directly apply the SIMEX idea to the pedigree. The initially known error proportion in the pedigree is progressively increased, all models are refitted, and the observed trend in the quantities of interest is extrapolated back to a hypothetical error‐free pedigree to obtain bias‐corrected estimates. We tested this pedigree‐SIMEX (PSIMEX) method with simulated pedigrees and with data from a free‐living population of song sparrows. The simulation study indicates that the PSIMEX estimator is almost unbiased for inbreeding depression and heritability, and that it has a much lower mean squared error (MSE) than the naive estimator. In the application to the song sparrows, the error‐corrected results could be validated against the actual values thanks to the availability of both an error‐prone and an error‐free pedigree. The results indicate that bias and MSE are reduced by PSIMEX. For easy accessibility of the method, we provide the R‐package PSIMEX. By transferring the SIMEX philosophy to error in pedigrees, we have illustrated how this heuristic approach can be generalized to situations where explicit error models are difficult to formulate. Thanks to the simplicity of the idea, many other error problems in ecology and evolution might be amenable to SIMEX‐like error correction methods.

Genome-wide estimation of inbreeding coefficient, effective population size and haplotype blocks in Vrindavani crossbred cattle strain of India

ABSTRACT In the present study, to analyze the genomic ROH fragments, haplotypes, inbreeding coefficient and effective population size (N e ), SNP50K data of 72 Vrindavani crossbred cattle strain were obtained. After a quality check, 24,449 biallelic SNPs were retained, which were in HWE, MAF > 0.01 and genotyping rate >95%. A total of 385 ROH were found, and chromosome 25 was mostly covered with 50.86%, while chromosome one was least with 12.42%. We classified ROH into <10Mb, 10-15Mb, 15-20Mb, >20Mb categories and observed a 3% inbreeding coefficient for the population in >20Mb category. Inbreeding from an excess of homozygosity was found to be 6% in the population. Ne was also estimated through N e Estimator and SNeP and in the recent generation, it was found to be 40 for a census size of 464 cattle. The Ne/Nc ratio was found to be 0.086 and a decreasing trend of Ne was observed for over five generations. 45.95% of the autosomal genome was covered with haplotypic structure with highest total block length in chromosome one and lowest in 28. From all the observations made in this study, it can be concluded that Vrindavani is an admixed cattle strain but have an unstable population structure in the current period.

Microsatellite analysis of golden grey mullet Chelon auratus (Risso, 1810) in the Fereydoon-Kenar and Ramsar coasts (south Caspian Sea, Iran)

Abstract Genetic structure of golden grey mullet Chelon auratus investigated in the Fereydoon-Kenar and Ramsar coasts (south Caspian Sea, Iran), using 6 microsatellite markers designed for gray mullet (Mugil cephalus) and hand mullet (Liza haematocheila). A total of 60 samples of adult C. auratus were collected from these regions. All primer sets as polymorphic loci were used to analyze genetic variation. Analyses revealed that average of alleles (Na) per locus was 6.2 (range 3 to 9 alleles). All sampled regions contained private alleles. The average estimates of inbreeding coefficient (Fis) values of 6 microsatellites were positive. The average observed and expected heterozygosity was 0.394 and 0.743, respectively. Deviations from Hardy-Weinberg equilibrium were in all cases (P&lt;0.001). F-statistics (Fst) and gene flow (Nm) estimates in allele frequencies were 0.078 and 2.9, respectively. Fst estimates in AMOVA indicated significant genetic differentiation among regions (P&lt;0.01). Genetic distance was 0.679 indicating that the genetic difference among the studied populations is pronounced. The data generated in this study provides genetic variation and differentiation in populations of C. auratus in the southern Caspian Sea.

Genetic diversity of Greek sheep breeds and transhumant populations utilizing microsatellite markers

Genetic variation in 13 local sheep breeds, raised in different regions of Greece, was assessed using 10 polymorphic microsatellite markers and was compared with that of three transhumant populations from the Greek Prefectures of Epirus, Sterea Ellada and Thessaly. The total number of alleles per marker ranged from 8 to 32 alleles, and transhumant samples exhibited higher values for allelic number, observed/expected heterozygosity and allelic richness than the local ones. Estimates of inbreeding coefficient (FIS) were significant only in the transhumant population of Epirus (*P<0.05). The genetic differentiation of the native breeds was low (FST=4.9%), indicating admixture, though all analyses provided clear evidence for the isolation of Thraki and Sarakatsaniko breeds. Differentiation of the three transhumant populations was much lower (FST=0.2%), indicating a high rate of gene flow between them. The admixture analysis, using Bayesian methods, suggested that many different local breeds have been used for breeding purposes in each of the three transhumant populations. Among the breeds with high proportion of membership to transhumant farming was Karagouniko which, as already known from literature, is used for the upgrading of numerous sheep populations in Greece.

High level of inbreeding in final phase of 1000 Genomes Project.

The 1000 Genomes Project provides a unique source of whole genome sequencing data for studies of human population genetics and human diseases. The last release of this project includes more than 2,500 sequenced individuals from 26 populations. Although relationships among individuals have been investigated in some of the populations, inbreeding has never been studied. In this article, we estimated the genomic inbreeding coefficient of each individual and found an unexpected high level of inbreeding in 1000 Genomes data: nearly a quarter of the individuals were inbred and around 4% of them had inbreeding coefficients similar or greater than the ones expected for first-cousin offspring. Inbred individuals were found in each of the 26 populations, with some populations showing proportions of inbred individuals above 50%. We also detected 227 previously unreported pairs of close relatives (up to and including first-cousins). Thus, we propose subsets of unrelated and outbred individuals, for use by the scientific community. In addition, because admixed populations are present in the 1000 Genomes Project, we performed simulations to study the robustness of inbreeding coefficient estimates in the presence of admixture. We found that our multi-point approach (FSuite) was quite robust to admixture, unlike single-point methods (PLINK).

Valid estimates of individual inbreeding coefficients from marker-based pedigrees are not feasible in wild populations with low allelic diversity

Pedigrees are frequently recommended for estimating inbreeding coefficients (F PED ), but are error-prone due to missing behavioural data in wild populations. Genetic marker-based pedigrees have been suggested as a remedy to this problem, but their accuracy depends on the number and polymorphism of loci available, and the completeness of population sampling. We used simulations to examine how accuracy of marker-based pedigrees varies with number of loci and sampling regime when allelic diversity is low (2.2–4 alleles per locus in founders), as is often the case in threatened species. We also examined the impact of pedigree errors on the validity of F PED estimated from marker-based pedigrees. Our results indicate that accurate parentage assignments are only feasible if genotypes are available for all individuals that ever existed in the population, and that accuracy does not improve past 40 loci. Errors in marker-based pedigrees resulted in underestimation of F PED by up to 27 % and overestimation of the variance in F PED by up to 182 %. At least 80 % pedigree accuracy was required to produce unbiased estimates of F PED , which were still highly imprecise. Given the degree of sampling required, it is not currently feasible to measure inbreeding in wild populations of threatened species with a pedigree based solely on microsatellite data. Resources may be better directed towards developing more robust genetic tools (whole genome sequencing and large SNP panels) to facilitate direct estimation of inbreeding coefficients without a pedigree. Where this is not possible, long-term monitoring projects will be required to accurately estimate inbreeding coefficients via a combination of behavioural and genetic data.

The effect of rare alleles on estimated genomic relationships from whole genome sequence data.

BackgroundRelationships between individuals and inbreeding coefficients are commonly used for breeding decisions, but may be affected by the type of data used for their estimation. The proportion of variants with low Minor Allele Frequency (MAF) is larger in whole genome sequence (WGS) data compared to Single Nucleotide Polymorphism (SNP) chips. Therefore, WGS data provide true relationships between individuals and may influence breeding decisions and prioritisation for conservation of genetic diversity in livestock. This study identifies differences between relationships and inbreeding coefficients estimated using pedigree, SNP or WGS data for 118 Holstein bulls from the 1000 Bull genomes project. To determine the impact of rare alleles on the estimates we compared three scenarios of MAF restrictions: variants with a MAF higher than 5%, variants with a MAF higher than 1% and variants with a MAF between 1% and 5%.ResultsWe observed significant differences between estimated relationships and, although less significantly, inbreeding coefficients from pedigree, SNP or WGS data, and between MAF restriction scenarios. Computed correlations between pedigree and genomic relationships, within groups with similar relationships, ranged from negative to moderate for both estimated relationships and inbreeding coefficients, but were high between estimates from SNP and WGS (0.49 to 0.99). Estimated relationships from genomic information exhibited higher variation than from pedigree. Inbreeding coefficients analysis showed that more complete pedigree records lead to higher correlation between inbreeding coefficients from pedigree and genomic data. Finally, estimates and correlations between additive genetic (A) and genomic (G) relationship matrices were lower, and variances of the relationships were larger when accounting for allele frequencies than without accounting for allele frequencies.ConclusionsUsing pedigree data or genomic information, and including or excluding variants with a MAF below 5% showed significant differences in relationship and inbreeding coefficient estimates. Estimated relationships and inbreeding coefficients are the basis for selection decisions. Therefore, it can be expected that using WGS instead of SNP can affect selection decision. Inclusion of rare variants will give access to the variation they carry, which is of interest for conservation of genetic diversity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0185-0) contains supplementary material, which is available to authorized users.

Detecting inbreeding depression for reproductive traits in Iberian pigs using genome-wide data.

BackgroundThe current availability of genotypes for very large numbers of single nucleotide polymorphisms (SNPs) is leading to more accurate estimates of inbreeding coefficients and more detailed approaches for detecting inbreeding depression. In the present study, genome-wide information was used to detect inbreeding depression for two reproductive traits (total number of piglets born and number of piglets born alive) in an ancient strain of Iberian pigs (the Guadyerbas strain) that is currently under serious danger of extinction.MethodsA total of 109 sows with phenotypic records were genotyped with the PorcineSNP60 BeadChip v1. Inbreeding depression was estimated using a bivariate animal model in which the inbreeding coefficient was included as a covariate. We used two different measures of genomic inbreeding to perform the analyses: inbreeding estimated on a SNP-by-SNP basis and inbreeding estimated from runs of homozygosity. We also performed the analyses using pedigree-based inbreeding.ResultsSignificant inbreeding depression was detected for both traits using all three measures of inbreeding. Genome-wide information allowed us to identify one region on chromosome 13 associated with inbreeding depression. This region spans from 27 to 54 Mb and overlaps with a previously detected quantitative trait locus and includes the inter-alpha-trypsin inhibitor gene cluster that is involved with embryo implantation.ConclusionsOur results highlight the value of high-density SNP genotyping for providing new insights on where genes causing inbreeding depression are located in the genome. Genomic measures of inbreeding obtained on a SNP-by-SNP basis or those based on the presence/absence of runs of homozygosity represent a suitable alternative to pedigree-based measures to detect inbreeding depression, and a useful tool for mapping studies. To our knowledge, this is the first study in domesticated animals using the SNP-by-SNP inbreeding coefficient to map specific regions within chromosomes associated with inbreeding depression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-014-0081-5) contains supplementary material, which is available to authorized users.

Consanguinity and its sociodemographic differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan.

Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe.

Population-Genetic Influences on Genomic Estimates of the Inbreeding Coefficient: A Global Perspective

Background/Aims: Culturally driven marital practices provide a key instance of an interaction between social and genetic processes in shaping patterns of human genetic variation, producing, for example, increased identity by descent through consanguineous marriage. A commonly used measure to quantify identity by descent in an individual is the inbreeding coefficient, a quantity that reflects not only consanguinity, but also other aspects of kinship in the population to which the individual belongs. Here, in populations worldwide, we examine the relationship between genomic estimates of the inbreeding coefficient and population patterns in genetic variation. Methods: Using genotypes at 645 microsatellites, we compare inbreeding coefficients from 5,043 individuals representing 237 populations worldwide to demographic consanguinity frequency estimates available for 26 populations as well as to other quantities that can illuminate population-genetic influences on inbreeding coefficients. Results: We observe higher inbreeding coefficient estimates in populations and geographic regions with known high levels of consanguinity or genetic isolation and in populations with an increased effect of genetic drift and decreased genetic diversity with increasing distance from Africa. For the small number of populations with specific consanguinity estimates, we find a correlation between inbreeding coefficients and consanguinity frequency (r = 0.349, p = 0.040). Conclusions: The results emphasize the importance of both consanguinity and population-genetic factors in influencing variation in inbreeding coefficients, and they provide insight into factors useful for assessing the effect of consanguinity on genomic patterns in different populations.

Statistical Inference for Hardy-Weinberg Proportions in the Presence of Missing Genotype Information

In genetic association studies, tests for Hardy-Weinberg proportions are often employed as a quality control checking procedure. Missing genotypes are typically discarded prior to testing. In this paper we show that inference for Hardy-Weinberg proportions can be biased when missing values are discarded. We propose to use multiple imputation of missing values in order to improve inference for Hardy-Weinberg proportions. For imputation we employ a multinomial logit model that uses information from allele intensities and/or neighbouring markers. Analysis of an empirical data set of single nucleotide polymorphisms possibly related to colon cancer reveals that missing genotypes are not missing completely at random. Deviation from Hardy-Weinberg proportions is mostly due to a lack of heterozygotes. Inbreeding coefficients estimated by multiple imputation of the missings are typically lowered with respect to inbreeding coefficients estimated by discarding the missings. Accounting for missings by multiple imputation qualitatively changed the results of 10 to 17% of the statistical tests performed. Estimates of inbreeding coefficients obtained by multiple imputation showed high correlation with estimates obtained by single imputation using an external reference panel. Our conclusion is that imputation of missing data leads to improved statistical inference for Hardy-Weinberg proportions.

Estimation of inbreeding coefficient and its effects on birth weight and kid survival in Markhoz goats

Estimation of inbreeding coefficient and its effects on birth weight and kid survival in Markhoz goats