利用高密度SNP标记分析中国荷斯坦牛基因组近交

畜禽育种中传统上利用系谱信息评估群体近交程度?近年来随着高通量单核苷酸多态(single nucleotide polymorphism, SNP)检测成本降低,使利用基因组信息分析真实的基因组近交程度成为可能?本研究利用牛54 K SNP 芯片数据统计了北京地区2107头荷斯坦牛基因组上的长纯合片段(runs of homozygosity, ROH)的频率和分布,计算了2种基因组近交系数,即染色体上ROH的长度占基因组总长度的比例(Froh)及个体所有标记基因型中纯合子所占比例,即基因组纯合度(Fhom),进而分析了两种基因组近交系数之间的相关性以及基因组近交与系谱近交系数之间的相关性?结果表明,共检测到44 676个ROH片段,其长度主要分布在1~10 Mb之间?不同长度的ROH散布于个体基因组内,短ROH较长ROH更为常见?ROH在染色体上并非均匀分布,ROH频率最高的区域为10号染色体中部?两种基因组近交系数之间相关性很高(91%以上),但基因组近交与系谱近交之间的相关性较低(低于50%)?系谱完整性是影响基因组近交与系谱近交结果一致的重要因素,基因组近交系数能够反映个体真实的近交,本研究为评估群体近交水平提供了有力工具?     

个体近交系数的BASIC电算程序

在高等动植物的遗传改良中,人们经常通 过近交选育出遗传优秀的个体。为度量生物个 体的近交程度,需要根据谱系估计生物个体的 近交系数。估计个体近交系数的一般原理和方 法已经解决,有关论述可参阅吴仲贤著《统计遗 传学》一书。本文主要是依据一般原理和方法, 研讨如何应用微型电子计算机准确、快速地计 算出任何系谱上全部个体的近交系数以及全部 个体间的亲缘系数,并提供各种型号微型机均 可使用的BASIC 语言软件程序与具体方法。     

个体近交系数的BASIC电算程序

在高等动植物的遗传改良中,人们经常通过近交选育出遗传优秀的个体。为度量生物个体的近交程度,需要根据谱系估计生物个体的近交系数。估计个体近交系数的一般原理和方法已经解决,有关论述可参阅吴仲贤著《统计遗传学》一书。本文主要是依据一般原理和方法,     

我国6个地方绵羊品种微卫星DNA多态性研究

利用聚丙烯酰胺凝胶电泳技术研究了我国蒙古羊、乌珠穆沁羊、哈萨克羊、阿勒泰羊、滩羊和藏绵羊 6个地方绵羊品种 17个微卫星标记的多态性 ,以探讨其遗传多样性、起源分化及群体间的遗传亲缘关系。结果表明微卫星标记不同位点间遗传多样性差异极显著 (P <0 0 1) ,群体间多态信息含量 (PIC)、近交程度 (Fis)和观察杂合度 (Obs .Het)差异不显著 ,但基因多样性 (genediversity)和期望杂合度 (Exp .Het)差异显著 (P <0 0 5 )。所研究的我国 6个地方绵羊品种与欧洲品种具有相似的遗传多样性 ,但具有较高的近交系数。个体和群体的聚类分析结果提示我国地方绵羊品种可能起源于两类祖先。群体间的聚类分析结果还表明 ,蒙古羊与乌珠穆沁羊分化不明显且具有较近的遗传亲缘关系 ,蒙古羊与藏绵羊间分化明显且具有较远的遗传亲缘关系。滩羊、阿勒泰羊以及藏绵羊间也具有较近的遗传亲缘关系。所研究的我国 6个地方绵羊品种的遗传分化 (Fst)与西班牙绵羊品种接近 ,但明显小于欧洲其他绵羊品种     

性状遗传力与QTL方差对标记辅助选择效果的影响

在采用动物模型标记辅助最佳线性无偏预测方法对个体育种值进行估计的基础上,模拟了在一个闭锁群体内连续对单个性状选择10个世代的情形,并系统地比较了性状遗传力和QTL方差对标记辅助选择所获得的遗传进展、QTL增效基因频率和群体近交系数变化的影响。结果表明：在对高遗传力和QTL方差较小的性状实施标记辅助选择时,可望获得更大的遗传进展;遗传力越高,QTL方差越大,则QTL增效基因频率的上升速度越快;遗传力较高时,群体近交系数上升的速度较为缓慢,而QTL方差对群体近交系数上升速度的影响则不甚明显。结合前人关于标记辅助选择相对效率的研究结果,可以认为：当选择性状的遗传力和QTL方差为中等水平时,标记辅助选择可望获得理想的效果。     

动物基因组选配方法与应用

基因组选择(genomic selection, GS)是利用覆盖基因组的分子标记预测动物个体的估计育种值,可以提高选择的准确度和选择强度,缩短世代间隔,做到早选、准选,使动物育种发生了巨大变革。过去的10多年间,基因组选择技术应用于奶牛等动物的育种中,使种用动物的选择更为准确,遗传进展得到大幅提高。但基因组选择通常重视目标性状的遗传进展,而忽略了配种亲本个体间的遗传关系,因此也没有考虑到后代群体中近交程度的增加、遗传多样性的降低以及有害基因的纯合等问题,因此难以维持长期的遗传进展。2016年,一种具有可持续性的遗传选择方法被正式提出,称为基因组选配(genomicmating,GM)。该方法利用待选种用个体的基因组信息实施优化的选种和选配,可以控制群体近交的增长速率,实现长期且可持续的遗传进展。因此基因组选配方法比基因组选择的方法更适合于现代动物育种,尤其适用于地方品种的保护和遗传改良。本文综述了基因组选配的基本概念、方法和应用,并通过模拟的方法比较了6种选配方案的选择效果,旨在为动物育种方法的应用提供参考。     

利用SNP芯片信息评估新疆近交牛基因组纯合度

新疆近交牛是经45年近亲繁育形成的近交群体,但由于繁育记录缺失,其原始亲本品种未知。为了明确新疆近交牛的遗传背景,并探索利用基因组信息评价牛群近交水平的可行性,本研究利用该群体及荷斯坦牛、新疆褐牛和哈萨克牛等16个国内外牛品种的SNP芯片数据,应用主成分分析和Admixture方法对塔城地区新疆近交牛的群体结构进行分析;通过进一步计算新疆近交牛、荷斯坦牛、新疆褐牛和哈萨克牛的群体遗传学参数以及基因组近交指标评估各群体近交程度;结合新疆近交牛的体型分类和基因组近交指标信息,探讨了个体近交程度与体型表现的关系;最后,基于对新疆近交牛和哈萨克牛高频长纯合片段区域的筛选,鉴定了新疆近交牛基因组特征区域。研究结果显示,新疆近交牛的遗传背景与哈萨克牛基本一致,近交牛基因组纯合程度明显高于其他群体,且基因纯合率越高的近交牛其体型越小,在一定程度上呈现了近交衰退对体型的影响。本研究还鉴定到与新疆近交牛基因组特征区域相关的6个基本生物学通路以及与重要经济性状相关的32个数量基因座(quantitative trait loci, QTL)。本研究结果为新疆近交牛这一特殊遗传资源的育种规划及未来该群体的开发利用提供了科学依据。     

不同QTL增效基因初始频率下标记辅助选择的效果

采用随机模拟方法模拟了在一个闭锁群体内连续对单个性状选择10个世代的情形。在假定选择性状受一个位于常染色体上的QTL和多基因共同控制的情况下,采用动物模型标记辅助最佳线性无偏预测方法估计个体育种值并据此进行种畜的选留,并在此基础上系统地比较了QTL增效基因初始频率对标记辅助选择效果的影响。结果表明：当群体中QTL增效基因的初始频率较低时,选择所获得的QTL基因型值的进展会更大,标记辅助选择在单位时间内可获得较大的遗传进展;此时,尽管QTL增效基因在群体中固定所需的世代数会更长一些,但其频率上升的速度却更快。而QTL增效基因初始频率的高低对群体近交增量的影响不是很大。     

大黄鱼连续两代雌核发育群体的微卫星标记分析

通过对大黄鱼(Pseudosciaena crocea)异质雌核发育一代群体(meio-G1)与二代群体(meio-G2)微卫星位点的纯合度进行分析,研究异质雌核发育对大黄鱼基因纯化的效率。结果显示:meio-G1和meio-G215个微卫星座位的平均纯合度分别为0.661和0.803,纯合位点比例最高个体分别为0.867(13/15)和0.933(14/15),两个群体内个体间的平均相似系数分别为0.5903和0.8672,最高分别达0.9286和1.0(遗传距离为0.0741和0),远高于两性交配繁殖群体(平均纯合度0.376,平均相似系数0.4687,个体间最小遗传距离0.2288);其中meio-G2群体有7个位点(46.7%)已经完全纯合固定,并与普通养殖群体产生较明显的遗传分化;表明人工诱导异质雌核发育可大大加速大黄鱼大多数基因位点的纯合,是快速建立高纯品系的有效手段。但不同位点的纯合度差异很大,部分位点在异质雌核发育后代中迅速纯合,在meio-G1中就达到很高的纯合度,而有些位点则在meio-G1和meio-G2中仍保持很高的杂合度;meio-G1和meio-G2群体中不同个体纯合位点比例差异也很大。研究培育的雌核发育群体为大黄鱼进一步选育提供了良好的遗传材料。       

中国10个地方猪种的群体近交程度分析

利用微卫星标记估计了中国10个地方猪种的群体近交系数。结果表明: 在随机交配群体中, 贵州小型香猪的近交系数最高为0.1992, 汉中黑猪的近交系数最低为0.0727。F检验表明, 品种间近交系数的差异不显著(P>0.05)。在近交群体中, 贵州小型香猪近交系和巴马香猪近交系的近交系数分别为0.5907和0.4761。     

Inbreeding avoidance in an isolated indigenous Zapotec community in the valley of Oaxaca, southern Mexico

We analyzed inbreeding using surname isonymy in an indigenous genetic isolate. The subjects were residents of a rural Zapotec-speaking community in the valley of Oaxaca, southern Mexico. The community can be classified as a genetic isolate with an average gene flow of < or = 3% per generation. Surnames were collected for individuals in each household in pedigree form using the culturally traditional patronym-matronym naming. Estimation of inbreeding from surname isonymy is facilitated by the traditional patronym-matronym name assignment among indigenous Mexican populations. A total of 2,149 individuals had valid surname patronym-matronym pairings, including 484 deceased ancestors. Surname isonymy analysis methods were used to estimate total inbreeding and to segregate it into random and nonrandom components. The surname isonymy coefficient computed from 119 isonymous surname pairings (119/2,149) was 0.0554. The estimated inbreeding coefficient from surname isonymy was 0.0138 (0.0554/4). The random and nonrandom components of inbreeding were F(r) = 0.0221 and F(n) = -0.0091, respectively. The results suggest that consanguinity is culturally avoided. Nonrandom inbreeding decreased total inbreeding by about 41%. Total estimated inbreeding by surname isonymy was 0.0138, which is similar to inbreeding estimated from a sample of pedigrees, 0.01. Socially prescribed inbreeding avoidance substantially lowered total F through negative nonrandom inbreeding. Even in the situation of genetic isolation and small effective population size (N(e)), estimated inbreeding is lower than may have otherwise occurred if inbreeding were only random. However, among the poorest individuals, socially prescribed jural rules for inbreeding avoidance failed to operate. Thus the preponderance of inbreeding appears to occur among the poor, economically disadvantaged in the community.     

Pedigree analysis and inbreeding effects over morphological traits in Campolina horse population

Genetic improvement, without control of inbreeding, can go to loss of genetic variability, reducing the potential for genetic gains in the domestic populations. The aim of this study was to analyze the population structure and the inbreeding depression in Campolina horses. Phenotype information from 43 465 individuals was analyzed, data provided by the Campolina Breeders Association. A pedigree file containing 107 951 horses was used to connected the phenotyped individuals. The inbreeding coefficient was performed by use of the diagonal of the relationship matrix and the genealogical parameters were computed using proper softwares. The effective population size was estimated based on the rate of inbreeding and census information, and the stratification of the population was verified by the average relationship coefficient between animals born in different regions of Brazil. The effects of inbreeding on morphological traits were made by the use of inbreeding coefficient as a covariate in the model of random regression. The inbreeding coefficient increased from 1990 on, impacting effective population size and, consequently, shrinking genetic variability. The paternal inbreeding was greater than maternal, which may be attributed to the preference for inbred animals in reproduction. The average genetic relationship coefficient of animals born in different states was lower than individuals born within the same state. The increase in the inbreeding coefficient was negatively associated with all studied traits, showing the importance to avoid genetic losses in the long term. Although results do not indicate a severe narrowing of the population until the present date, the average relationship coefficient shows signs of increase, which could cause a drastic reduction in genetic variability if inbred mating is not successfully controlled in the Campolina horse population.     

Efficiency of selection, as measured by single nucleotide polymorphism variation, is dependent on inbreeding rate in Drosophila melanogaster

It is often hypothesized that slow inbreeding causes less inbreeding depression than fast inbreeding at the same absolute level of inbreeding. Possible explanations for this phenomenon include the more efficient purging of deleterious alleles and more efficient selection for heterozygote individuals during slow, when compared with fast, inbreeding. We studied the impact of inbreeding rate on the loss of heterozygosity and on morphological traits in Drosophila melanogaster. We analysed five noninbred control lines, 10 fast inbred lines and 10 slow inbred lines; the inbred lines all had an expected inbreeding coefficient of approximately 0.25. Forty single nucleotide polymorphisms in DNA coding regions were genotyped, and we measured the size and shape of wings and counted the number of sternopleural bristles on the genotyped individuals. We found a significantly higher level of genetic variation in the slow inbred lines than in the fast inbred lines. This higher genetic variation was resulting from a large contribution from a few loci and a smaller effect from several loci. We attributed the increased heterozygosity in the slow inbred lines to the favouring of heterozygous individuals over homozygous individuals by natural selection, either by associative over‐dominance or balancing selection, or a combination of both. Furthermore, we found a significant polynomial correlation between genetic variance and wing size and shape in the fast inbred lines. This was caused by a greater number of homozygous individuals among the fast inbred lines with small, narrow wings, which indicated inbreeding depression. Our results demonstrated that the same amount of inbreeding can have different effects on genetic variance depending on the inbreeding rate, with slow inbreeding leading to higher genetic variance than fast inbreeding. These results increase our understanding of the genetic basis of the common observation that slow inbred lines express less inbreeding depression than fast inbred lines. In addition, this has more general implications for the importance of selection in maintaining genetic variation.     

Gene flow and inbreeding depression inferred from fine-scale genetic structure in an endangered heterostylous perennial, Primula sieboldii

We estimated the gene dispersal distance and the magnitude of inbreeding depression from the fine-scale genetic structure in the endangered heterostylous perennial Primula sieboldii. We indirectly estimated the neighbourhood size (Nb) and the standard deviation of gene dispersal distance (sigma(g)) from the detected genetic structure by using 10 microsatellite markers. We also estimated the fitness reduction in mating among neighbouring individuals caused by biparental inbreeding according to the genetic structure. We found clear fine-scale genetic structure (a significantly positive kinship coefficient within 42.3 m), and the indirect estimates of sigma(g) and Nb were 15.7 m and 50.9, respectively. These indirect estimates were similar to the direct estimates (18.4 m and 44.0). The slightly larger indirect estimate of Nb may reflect that inbreeding depression and genetic structure or rare long-distance dispersal that were overlooked in the direct estimate have elongated the long-term average of gene dispersal distance. P. sieboldii is also likely to suffer about 19% fitness reduction in progenies from mating among individuals 5 m apart. Our results suggest that biparental inbreeding and genetic structure can affect the range of gene dispersal and seed reproductive success in P. sieboldii.     

The effect of genomic information on optimal contribution selection in livestock breeding programs

Background

Long-term benefits in animal breeding programs require that increases in genetic merit be balanced with the need to maintain diversity (lost due to inbreeding). This can be achieved by using optimal contribution selection. The availability of high-density DNA marker information enables the incorporation of genomic data into optimal contribution selection but this raises the question about how this information affects the balance between genetic merit and diversity.

Methods

The effect of using genomic information in optimal contribution selection was examined based on simulated and real data on dairy bulls. We compared the genetic merit of selected animals at various levels of co-ancestry restrictions when using estimated breeding values based on parent average, genomic or progeny test information. Furthermore, we estimated the proportion of variation in estimated breeding values that is due to within-family differences.

Results

Optimal selection on genomic estimated breeding values increased genetic gain. Genetic merit was further increased using genomic rather than pedigree-based measures of co-ancestry under an inbreeding restriction policy. Using genomic instead of pedigree relationships to restrict inbreeding had a significant effect only when the population consisted of many large full-sib families; with a half-sib family structure, no difference was observed. In real data from dairy bulls, optimal contribution selection based on genomic estimated breeding values allowed for additional improvements in genetic merit at low to moderate inbreeding levels. Genomic estimated breeding values were more accurate and showed more within-family variation than parent average breeding values; for genomic estimated breeding values, 30 to 40% of the variation was due to within-family differences. Finally, there was no difference between constraining inbreeding via pedigree or genomic relationships in the real data.

Conclusions

The use of genomic estimated breeding values increased genetic gain in optimal contribution selection. Genomic estimated breeding values were more accurate and showed more within-family variation, which led to higher genetic gains for the same restriction on inbreeding. Using genomic relationships to restrict inbreeding provided no additional gain, except in the case of very large full-sib families.     

On the use of large marker panels to estimate inbreeding and relatedness: empirical and simulation studies of a pedigreed zebra finch population typed at 771 SNPs

In recent years there has been a dramatic increase in the availability of high density genetic marker data for both model and non‐model organisms. A potential application of these data is to infer relatedness in the absence of a complete pedigree. Using a marker panel of 771 SNPs genotyped in three generations of an extensive zebra finch pedigree, correlations between pedigree relatedness and seven marker‐based estimates of relatedness were examined, as was the relationship between heterozygosity and inbreeding. Although marker‐based and pedigree relatedness were highly correlated, the variance in estimated relatedness was high. Further, the correlation between heterozygosity and inbreeding was weak, even though mean inbreeding coefficient is typical of that seen in wild vertebrate pedigrees; the weak relationship was in part due to the small variance in inbreeding in the pedigree. Our data suggest that using marker information to reconstruct the pedigree, and then calculating relatedness from the pedigree, is likely to give more accurate relatedness estimates than using marker‐based estimators directly.     

Accounting for cryptic population substructure enhances detection of inbreeding depression with genomic inbreeding coefficients: an example from a critically endangered marsupial

Characterizing inbreeding depression in wildlife populations can be critical to their conservation. Coefficients of individual inbreeding can be estimated from genome‐wide marker data. The degree to which sensitivity of inbreeding coefficients to population genetic substructure alters estimates of inbreeding depression in wild populations is not well understood. Using generalized linear models, we tested the power of two frequently used inbreeding coefficients that are calculated from genome‐wide SNP markers, F_H and F^^III, to predict four fitness traits estimated over two decades in an isolated population of the critically endangered Leadbeater's possum. F_H estimates inbreeding as excess observed homozygotes relative to equilibrium expectations, whereas F^^III quantifies allelic similarity between the gametes that formed an individual, and upweights rare homozygotes. We estimated F_H and F^^III from 1,575 genome‐wide SNP loci in individuals with fitness trait data (N = 179–237 per trait), and computed revised coefficients, F_H^{by group} and F^^{IIIby group}, adjusted for population genetic substructure by calculating them separately within two different genetic groups of individuals identified in the population. Using F_H or F^^III in the models, inbreeding depression was detected for survival to sexual maturity, longevity and whether individuals bred during their lifetime. F^^{IIIby group} (but not F_H^{by group}) additionally revealed significant inbreeding depression for lifetime reproductive output (total offspring assigned to each individual). Estimates of numbers of lethal equivalents indicated substantial inbreeding load, but differing between inbreeding estimators. Inbreeding depression, declining population size, and low and declining genetic diversity suggest that genetic rescue may assist in preventing extinction of this unique Leadbeater's possum population.     

Genome-Wide Estimates of Coancestry and Inbreeding in a Closed Herd of Ancient Iberian Pigs

Maintaining genetic variation and controlling the increase in inbreeding are crucial requirements in animal conservation programs. The most widely accepted strategy for achieving these objectives is to maximize the effective population size by minimizing the global coancestry obtained from a particular pedigree. However, for most natural or captive populations genealogical information is absent. In this situation, microsatellites have been traditionally the markers of choice to characterize genetic variation, and several estimators of genealogical coefficients have been developed using marker data, with unsatisfactory results. The development of high-throughput genotyping techniques states the necessity of reviewing the paradigm that genealogical coancestry is the best parameter for measuring genetic diversity. In this study, the Illumina PorcineSNP60 BeadChip was used to obtain genome-wide estimates of rates of coancestry and inbreeding and effective population size for an ancient strain of Iberian pigs that is now in serious danger of extinction and for which very accurate genealogical information is available (the Guadyerbas strain). Genome-wide estimates were compared with those obtained from microsatellite and from pedigree data. Estimates of coancestry and inbreeding computed from the SNP chip were strongly correlated with genealogical estimates and these correlations were substantially higher than those between microsatellite and genealogical coefficients. Also, molecular coancestry computed from SNP information was a better predictor of genealogical coancestry than coancestry computed from microsatellites. Rates of change in coancestry and inbreeding and effective population size estimated from molecular data were very similar to those estimated from genealogical data. However, estimates of effective population size obtained from changes in coancestry or inbreeding differed. Our results indicate that genome-wide information represents a useful alternative to genealogical information for measuring and maintaining genetic diversity.     

Inbreeding depression for various traits in two cultured populations of the American bay scallop, Argopecten irradians irradians Lamarck (1819) introduced into China

This paper examines the effect of inbreeding level of population on the magnitude of inbreeding depression expressed by comparing them between two cultured populations (A and B) in the hermaphroditic animal of the bay scallop Argopecten irradians irradians. Population A is expected to have less genetic variations and higher inbreeding level due to longer cultured history (20 generations) and less “ancestral” individuals (26 individuals) than population B due to shorter cultured history (4 generations) and more “ancestral” individuals (406 individuals). Two groups within each population were produced, one using self-fertilization and one using mass-mating within the same population. Selfed offspring (AS and BS) from two populations both had lower fitness components than their mass-mated counterparts (AM and BM) and exhibited inbreeding depression for all examined traits, e.g. lower hatching, less viability and slower growth, indicating that inbreeding depression is a common feature in this animal. Fitness components in all traits of offspring from population A significantly differed those from population B and the magnitude of inbreeding depression for all traits in population A with higher inbreeding level was significantly smaller than that in population B with lower inbreeding level, indicating that both fitness components and magnitude of inbreeding depression were significantly affected by inbreeding level of populations and genetic load harbored in population A may be partially purged through inbreeding. Moreover, the magnitude of inbreeding depression in the two populations both varied among traits and life history stages. The present results support the partial-dominance hypothesis of inbreeding depression.