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

Background: Runs 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.Results: In 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_totaland FHOM, while the lowest was-0.083 between FGRMand FPED. The correlations between FPEDand FROHusing 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.Conclusion: FROHcan be used to accurately assess individual inbreeding levels compared to other inbreeding coefficient estimators. In the absence of pedigree records, FROHcan 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.

Genome-wide analysis of runs of homozygosity identifies new susceptibility regions of lung cancer in Han Chinese

Runs of homozygosity （ROHs） are a class of important but poorly studied genomic variations and may be in- volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung cancer, we performed a genome-wide ROH analysis of a subset of a previous genome-wide case-control study （1,473 cases and 1,962 controls） in a Han Chinese population. ROHs were classified into two classes, based on lengths, intermedi- ate and long ROils, to evaluate their association with lung cancer risk using existing genome-wide single nucleofide polymorphism （SNP） data. We found that the overall level of intermediate ROHs was significantly associated with a decreased risk of lung cancer （odds ratio = 0.63; 95% confidence interval： 0.51-0.77; P = 4.78 × 10-6 ）, while the long ROHs seemed to be a risk factor of lung cancer. We also identified one ROH region at 14q23A that was con- sistently associated with lung cancer risk in the study. These results indicated that ROHs may be a new class of variation which may be associated with lung cancer risk, and genetic variants at 14q23.1 may be involved in the development of lung cancer.

Genome-wide detection for runs of homozygosity analysis in three pig breeds from Chinese Taihu Basin and Landrace pigs by SLAF-seq data

Erhualian(E),Meishan(MS)and Mi(MI)pigs are excellent indigenous pig breeds in Chinese Taihu Basin,which have made great contributions to the genetic improvement of commercial pigs.Investigation of the genetic structure and inbreeding level of the 3 pig breeds is of great significance for the sustainable breeding of commercial pigs.The length and number of runs of homozygosity(ROH)as well as the frequency of genomes covered by ROH can be used as indicators to evaluate the level of inbreeding and the origin of the population.In this study,the ROH characteristics of E,MS,MI and Landrace(L)pigs were analyzed by SLAF-seq data,and the inbreeding coefficient based on ROH(F_(ROH))was calculated.In addition,we have identified candidate genes in the genomic regions associated with ROH.A total of10568 ROH were detected in 116 individuals of 4 pig breeds.The analysis showed that there were significant differences in genetic structure between 3 Taihu Basin pig breeds and L,and the genetic structure of E and MI was similar.The results of F_(ROH)showed that the inbreeding level of MS was the highest(0.25±0.07),while E and MI were lower than L.Compared with the other 3 pig populations,MS showed a higher frequency of long ROH(>5 Mb),indicating higher inbreeding in MS in recent generations.A large number of candidate genes related to reproductive traits are located in the genomic regions with a high frequency of ROH,and these genes are expected to be used as candidate genes in marker-assisted selection(MAS)breeding programs.Our findings can provide theoretical support for genetic conservation and genetic improvement of 3 pig breeds in Chinese Taihu Basin.

Conservation genomics provides insights into genetic resilience and adaptation of the endangered Chinese hazelnut, Corylus chinensis

Global climate change has increased concerns regarding biodiversity loss.However,many key conservation issues still required further research,including demographic history,deleterious mutation load,adaptive evolution,and putative introgression.Here we generated the first chromosome-level genome of the endangered Chinese hazelnut,Corylus chinensis,and compared the genomic signatures with its sympatric widespread C.kwechowensis-C yunnanensis complex.We found large genome rearrangements across all Corylus species and identified species-specific expanded gene families that may be involved in adaptation.Population genomics revealed that both C.chinensis and the C.kwechowensis-C.yunnanensis complex had diverged into two genetic lineages,forming a consistent pattern of southwestern-northern differentiation.Population size of the narrow southwestern lineages of both species have decreased continuously since the late Miocene,whereas the widespread northern lineages have remained stable(C.chinensis) or have even recovered from population bottlenecks(C.kwechowensis-C.yunnanensis complex) during the Quaternary.Compared with C.kwechowensis-C. yunnanensis complex,C.chinensis showed significantly lower genomic diversity and higher inbreeding level.However,C.chinensis carried significantly fewer deleterious mutations than C.kwechowensis-C. yunnanensis complex,as more effective purging selection reduced the accumulation of homozygous variants.We also detected signals of positive selection and adaptive introgression in different lineages,which facilitated the accumulation of favorable variants and formation of local adaptation.Hence,both types of selection and exogenous introgression could have mitigated inbreeding and facilitated survival and persistence of C.chinensis.Overall,our study provides critical insights into lineage differentiation,local adaptation,and the potential for future recovery of endangered trees.

ROH及其在绵羊遗传育种中的应用研究进展

连续性纯合片段(runs of homozygosity,ROH)是基因组中的一段长纯合片段,不同长度的ROH和个体与共同祖先的亲缘背景相关联,亲缘关系越远ROH片段越短。在近交过程中,随着世代数的增加,子代个体从共同祖先遗传得到的ROH会被不断地打断重排。在整个遗传信息传递过程中,可以根据ROH的长短来判断个体间亲缘关系的亲近程度。ROH受种群近交、种群瓶颈、基因组特征、人工选择等多种因素的制约,这些制约因素会在其基因组上留下各种印记。ROH中有丰富的遗传信息,促使ROH成为研究绵羊基因组信息的新手段。近年来,随着高通量测序技术的发展,研究人员利用基因组ROH来评估近交程度和遗传多样性、推断种群结构和种群历史、筛选和鉴定重要经济性状功能基因,进行个体选择并追踪选择信号。因此,笔者就ROH产生原理、影响因素、检测方法及其在绵羊遗传育种中的应用等方面进行综述,以期能准确制定绵羊种质资源保护策略,为ROH在绵羊遗传育种中的应用提供理论依据。

基于GBS测序的湘东黑山羊的亲缘关系及近交系数

利用基因分型测序(GBS)对60只湘东黑山羊(9只公羊、51只母羊)进行基因组测序,获得湘东黑山羊染色体上的SNP数据和连续纯合子片段(ROH)数据。通过SNP数据进行基于G矩阵的基因组亲缘关系分析和NJ聚类分析,构建湘东黑山羊的群体家系结构,并通过ROH数据得到群体平均近交系数。结果表明,60只湘东黑山羊的平均测序深度为9.15X,与参考基因组比对率平均为99.59%;在SNP检测过程中,3只母羊不符合基因型数据质控标准,将其过滤后获得其他57只黑山羊29条染色体上153046个SNPs位点和1937个ROH片段;构建的湘东黑山羊8个家系,其中9只公羊和6只母羊被分为7个家系,另42只母羊被单独分类;基于ROH片段分析的湘东黑山羊群体中每个个体的近交系数均值为0.047,说明湘东黑山羊公羊在繁育过程中有较大的利用空间。

利用“黄海芯1号”55K SNP芯片评估凡纳滨对虾选育群体的遗传多样性与基因组近交水平

凡纳滨对虾的主要选育目标分为两个方面:一是培育具有较强抗病、抗逆性的“高抗系”(GK),二是培育具有快速生长特性的“快大系”(KD)。然而,国内缺少针对这两个选育群体的遗传多样性特别是基因组近交水平的调查分析研究。基于液相芯片“黄海芯1号”(55 K SNP)的基因分型数据,首次分析了GK(1064尾个体)和KD(564尾个体)选育群体的遗传结构和遗传多样性,调查了连续性纯合片段(ROH)的基因组分布特征,并重点评估了两个群体的基因组近交水平。PCA及进化树分析表明GK及KD群体可明确分层,亲缘关系热图表明KD群体内个体间的亲缘关系比GK群体更近。GK群体包括的家系数量更多,导致其遗传多样性高于KD群体;两群体间的F_(st)为0.09,存在中等遗传分化。GK和KD群体每个ROH的平均长度分别为(1.70±0.34)Mb和(1.65±0.38)Mb,每个样本ROH的平均数量分别为1.98±1.30和2.07±1.37。GK和KD群体0.8~1.25 Mb长度的ROH占比分别为11.41%和19.17%,表明KD群体的选育历史比GK群体更长。两个群体>2.25 Mb长度的ROH片段占比分别为10.26和9.74%,表明两个群体短期内未发生近亲交配。七种基因组近交系数评估结果表明,KD群体的近交水平高于GK群体。不依赖基础群体等位基因频率的F_(ROH)和F_(HOM)方法可准确地评价育种群体的真实近交水平,而F_(VR1)、F_(YA1)和F_(LH1)等依赖基础群体等位基因频率的方法可以用来比较群体及个体间的相对近交水平。上述结果为准确地评估育种群体的近交水平和优化育种方案提供了重要参考依据。

枫泾猪、梅山猪和沙乌头猪全基因组ROH检测及候选基因鉴定

通过检测枫泾猪、梅山猪和沙乌头猪的长纯合片段(Runs of homozygosity,ROH),鉴定其与3个猪种经济性状相关的候选基因。利用全基因组单核苷酸多态性(Single Nucleotide Polymorphisms,SNP)芯片数据对这3个猪群体进行全基因组ROH检测,统计ROH数量、长度及分布,计算基于ROH的近交系数(FROH),并在高频ROH区域鉴定候选功能基因。结果显示,从枫泾猪、梅山猪和沙乌头猪群体中分别检测到1588个、3314个和4419个ROH。枫泾猪的ROH平均长度为12.84 Mb,平均FROH为0.084;梅山猪的ROH平均长度为10.55 Mb,平均FROH为0.164;沙乌头猪的ROH平均长度为10.52 Mb,平均FROH为0.141。在高频ROH区域共鉴定到9个枫泾猪候选功能基因和8个梅山猪候选功能基因。研究结果为枫泾猪、梅山猪和沙乌头猪的资源保护和分子标记辅助选择奠定了基础。

基于简化基因组测序评估陇南山羊群体遗传多样性和群体结构

该试验旨在利用简化基因组测序(specific-locus amplified fragment sequencing, SLAF-seq)分析陇南山羊群体遗传多样和群体结构,为陇南山羊后续保种计划的制订提供依据。该研究对50只陇南山羊(公、母各25只)进行全基因组SNP检测;计算观测杂合度(Ho)、期望杂合度(He)、多态信息含量(PIC)、香浓维纳指数(SHI)、基因多样性指数(Nei)及次要等位基因频率(MAF)等6个指标进行遗传多样性评估。结果表明,50只陇南山羊共检测到655514个SNPs位点。陇南山羊的Ho、 He、 PIC、 SHI、 Nei及MAF指标值分别为0.193、0.286、 0.236、 0.449、 0.290、 0.200,说明该群体遗传多样性较低。陇南山羊群体LD值较低,衰退速度较快,说明该群体并未受到过强烈的人工选择压力。此外,PCA与系统发育树结果均表明陇南山羊群体内部出现分化,可分为2个大的亚群。陇南山羊群体平均IBS遗传距离为0.7391,结合亲缘关系G矩阵热图,表明陇南山羊群体大部分个体亲缘关系较远。50只陇南山羊个体共检测到47206个ROH,平均ROH长度37.86 Mb,基于ROH的近交系数FROH范围为0.0535~0.2574,平均FROH值为0.1472,说明陇南山羊群体存在近交风险。可见,陇南山羊内部存在分化,可分为2个大的亚群,陇南山羊群体遗传多样性较低,部分个体间存在较大的近交风险,可能需要采取保种措施保护陇南山羊遗传资源。

Estimates of genomic inbreeding and identification of candidate regions that differ between Chinese indigenous sheep breeds

Background:A run of homozygosity(ROH)is a consecutive tract of homozygous genotypes in an individual that indicates it has inherited the same ancestral haplotype from both parents.Genomic inbreeding can be quantified based on ROH.Genomic regions enriched with ROH may be indicative of selection sweeps and are known as ROH islands.We carried out ROH analyses in five Chinese indigenous sheep breeds;Altay sheep(n=50 individuals),Large-tailed Han sheep(n=50),Hulun Buir sheep(n=150),Short-tailed grassland sheep(n=150),and Tibetan sheep(n=50),using genotypes from an Ovine Infinium HD SNP BeadChip.Results:A total of 18,288 ROH were identified.The average number of ROH per individual across the five sheep breeds ranged from 39(Hulun Buir sheep)to 78(Large-tailed Han sheep)and the average length of ROH ranged from 0.929 Mb(Hulun Buir sheep)to 2.544 Mb(Large-tailed Han sheep).The effective population size(Ne)of Altay sheep,Large-tailed Han sheep,Hulun Buir sheep,Short-tailed grassland sheep and Tibetan sheep were estimated to be 81,78,253,238 and 70 five generations ago.The highest ROH-based inbreeding estimate(FROH)was 0.0808 in Large-tailed Han sheep,whereas the lowest F_(ROH)was 0.0148 in Hulun Buir sheep.Furthermore,the highest proportion of long ROH fragments(>5 Mb)was observed in the Large-tailed Han sheep breed which indicated recent inbreeding.In total,49 ROH islands(the top 0.1% of the SNPs most commonly observed in ROH)were identified in the five sheep breeds.Three ROH islands were common to all the five sheep breeds,and were located on OAR2:12.2-12.3 Mb,OAR12:78.4-79.1 Mb and OAR13:53.0-53.6 Mb.Three breed-specific ROH islands were observed in Altay sheep(OAR15:3.4-3.8 Mb),Large-tailed Han sheep(ORA17:53.5-53.8 Mb)and Tibetan sheep(ORA5:19.8-20.2 Mb).Collectively,the ROH islands harbored 78 unique genes,including 19 genes that have been documented as having associations with tail types,adaptation,growth,body size,reproduction or immune response.Conclusion:Different ROH patterns were observed in five Chinese indigenous sheep breeds,which reflected their different population histories.Large-tailed Han sheep had the highest genomic inbreeding coefficients and the highest proportion of long ROH fragments indicating recent inbreeding.Candidate genes in ROH islands could be used to illustrate the genetic characteristics of these five sheep breeds.Our findings contribute to the understanding of genetic diversity and population demography,and help design and implement breeding and conservation strategies for Chinese sheep.

基于SNP芯片数据分析不同奶牛场基因组近交系数及筛选功能性基因

旨在利用基因组长纯合片段(runs of homozygosity,ROH)信息评估河南省不同中国荷斯坦牛群体的全基因组近交水平,并通过ROH检测鉴定基因组ROH富集区域,筛选与奶牛经济性状相关的候选基因。本研究基于GGP Bovine 150K芯片对来自河南省7个牧场900头荷斯坦牛进行全基因组ROH检测,统计ROH在荷斯坦群体中的数目、长度及频率,根据ROH计算基因组近交系数(F_(ROH)),并对高频ROH区域进行基因注释。结果表明,在全部900个体中共检测出55908个ROH片段,平均长度4.23 Mb。7个牧场平均近交系数(F_(ROH))的变化范围从0.082(H7)到0.123(H2),平均F_(ROH)为0.106。在ROH的高频区域内共鉴定到79个与奶牛经济性状相关的基因,如与牛体型、体高有关的基因AKAP3、C5H12orf4、FGF6,与胴体及繁殖性状相关的基因CAPN3,与妊娠维持和胎儿生长直接相关的基因CHST14,影响牛奶蛋白质组成的基因IL5RA,参与调节胎儿卵泡生成的基因FGF10。其中,在14号染色体上检测到一个高频率的ROH区域(22.78~23.38 Mb),超过80%的个体都在该区域内发生ROH片段,并在此区域鉴定到与生长和饲料转化率相关的基因TGS1、LYN、CHCHD7。基于ROH信息的奶牛近交评估可为奶牛场的选种选配提供指导,在高频ROH区域鉴定到的候选基因可作为奶牛分子育种中进行标记辅助选择的基因。

广西合浦珠母贝3个不同群体遗传关系分析

为探索广西合浦珠母贝群体内杂交组合方式,分别从北海野生群体(F_(1))、选育群体(F_(4))和养殖群体中随机挑选2龄种贝样本15个,进行简化基因组测序,通过单核苷酸多态标记解析3个群体的遗传关系。研究结果显示,获得超过585000个单核苷酸多态标记,野生群体、选育群体和养殖群体的观测杂合度分别为0.1975、0.1679和0.1783,期望杂合度分别为0.2545、0.2469和0.2732,平均近交系数分别为0.2075、0.3449和0.3465,多态信息含量分别为0.2032、0.2089和0.2241,选育群体近交系数与养殖群体相近,野生群体和养殖群体的群体遗传多态高于选育群体。系统进化树和主成分分析显示,选育群体与养殖群体部分样品亲缘关系较近。选育群体和养殖群体之间的遗传分化指数最低,部分亲本同源的可能性较大;野生群体、选育群体和养殖群体的平均长纯合片段数分别为59.1、49.5个和56.6个,长纯合片段平均长度分别为0.312、0.313Mb和0.311Mb,平均单核苷酸多态标记含量分别为59、50和73,近交系数FROH分别为0.0149~0.0240、0.0159~0.0201和0.0170~0.0246,反映3个群体的真实近交水平较低;野生群体、选育群体和养殖群体的整个染色体内连锁不平衡衰减距离分别为0.4、0.4kb和0.2kb(r2=0.2),衰减速度为养殖群体>野生群体>选育群体,选育群体衰减速度最慢,可能与人工选育有关。以上结果表明,广西合浦珠母贝可采用野生群体×选育群体或野生群体×养殖群体的杂交组合方式开展群体内杂交。本研究结果可为广西合浦珠母贝育种中的亲本选择提供参考。

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。

连续性纯合片段在畜禽基因组研究中的应用

随着高通量SNP芯片技术的快速发展和测序成本的大幅降低,SNP基因芯片和基因组重测序等技术被广泛地应用于畜禽基因组研究中。在基因组某一段区域内,当一定数量和一定密度的SNPs表现为纯合时,可以判定该区域存在连续性纯合片段(runs of homozygosity, ROH)。目前,连续性纯合片段已经逐渐成为分析畜禽群体近交程度、遗传结构等方面的重要指标之一。但是,ROH计算应用的评价标准还相对匮乏。本文系统介绍了连续性纯合片段的发展历史、原理、鉴定方法以及在畜禽群体结构解析、基因组功能分析和种畜禽品质检测等方面的应用情况,以期为畜禽遗传资源保种区和保种场在遗传多样性等动态监测方面提供参考。

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?

近交陆川猪的遗传稳定性研究

旨在探讨高度近交陆川猪的遗传稳定性。本试验采集20头近交和6头非近交陆川猪的耳组织样品进行个体基因组重测序,通过扫描全基因组SNPs分析近交陆川猪群体的遗传多样性,并基于基因组纯合度挖掘近交陆川猪群体中特异的纯合区域(region of homozygosity,ROHs)及相关基因。结果表明,近交陆川猪群体的观察杂合度(0.373)小于期望杂合度(0.491),推测其发生了选择或者近交;系统进化树和群体遗传结构分析发现,近交陆川猪群体在近交过程中分化成为两个近交家系,且230、236、239、132、130及126号个体亲缘关系最近;在近交群体中,基因组纯合度和基因组长纯合片段比例的均值分别为59.64%和0.12,都极显著高于非近交群体53.18%和0.05(P<0.01),说明该近交陆川猪群体已达到高度近交;近交群体和非近交群体中分别有1250和633个ROHs,重叠分析结果显示,特异存在于近交群体中的阳性纯合区域(positive region of homozygosity,pROHs)有224个,其中由于近交产生的纯合突变可能影响参与激素合成过程、胰液分泌、膜脂代谢过程、IgA产生的肠道免疫网络及纹肌细胞分化等相关的1322个基因。结果提示,近交陆川猪群体的遗传多样性低、基因组纯合度高且已达到高度近交,说明该群体的遗传稳定性高。此外,近交陆川猪群体在近交过程中产生的纯合突变可能与机体的免疫、生长等生产性状相关。

不同来源大白猪总产仔数近交衰退评估

旨在评估两个不同来源大白猪群体经过近8个世代的选育后总产仔数(total number of piglets born,TNB)近交衰退的程度。本研究对1937头大白猪使用GeneSeek GGP Porcine HD芯片进行分型,其中1039头来自加系大白猪和898头来自法系大白猪,且两品系均有表型记录和系谱记录,系谱共由3086头大白猪组成。分别使用系谱、SNP和ROH进行个体近交系数估计,并将近交系数作为协变量利用动物模型对总产仔数进行近交衰退评估。为了精准定位导致总产仔数衰退的基因组片段,又进一步对每条染色体以及显著染色体分段计算近交系数并估计其效应,检测是否能引起总产仔数发生近交衰退现象。对于加系群体,FROH、FGRM和FPED估计的近交系数均值分别为0.124、0.042和0.013,其中FROH和FPED相关最高,相关系数为0.358;对于法系群体,FROH、FGRM和FPED均值分别为0.123、0.052和0.007,其中FROH和FGRM相关最高,相关系数为0.371。利用3种不同计算方法所得近交系数用于估计近交衰退时,加系群体的总产仔数均检测到显著的近交衰退,而且当FROH、FGRM和FPED每增加10%时,总产仔数分别减少0.571、0.341和0.823头;但法系群体仅有FROH估计的总产仔数检测到显著近交衰退,FROH每增加10%时,总产仔数减少0.690头。为了锁定相关的染色体和基因组区段,首先利用ROH估计每条染色体近交系数并进行近交衰退分析发现,加系群体中检测到第6、7、8和13号染色体产生了显著近的总产仔数交衰退,而法系群体未检测到与近交衰退相关的染色体。然后,又将与加系总产仔数近交衰退显著相关的4条染色体平均分为2、4、6、8个片段进行近交衰退检测,其中平均分成8段后的染色片段的长度范围为15.1~25.8 Mb。在第6、7和8号染色体分别检测到1、2和3个与总产仔数相关的近交衰退染色体片段。这些区域注释到了CUL7、MAPK14和PPARD基因与胎盘发育相关,AREG和EREG基因与卵母细胞成熟有关。本研究利用3种近交系数计算方法对两个不同来源的大白猪总产仔数进行近交衰退评估,在加系大白猪中3种估计方法都能检测到近交衰退的现象,而法系群体中只有FROH才能检测到。而且通过ROH方法进一步确定了能引起加系大白猪总产仔数衰退的4条染色体和6个特定的染色体区段,还注释到了与繁殖相关的候选基因。这为揭示近交衰退的遗传机制提供了新的研究手段,也为基因组选种选配提供了参考依据。

畜禽全基因组长纯合片段检测的研究进展

长纯合片段(runs of homozygosity,ROH)是在个体和群体中常见的连续性纯合片段,是亲代将同源相同的单倍型遗传给同一个后代而形成的。ROH蕴藏着种群丰富的遗传信息,这使ROH成为一种有用的工具,可以提供关于种群是如何随着时间的演变而变化的信息。ROH也可以用于估计个体间遗传关系,有助于将近亲交配率降至最低,还可以暴露基因组中有害的变异。ROH在基因组中的大小、分布和频率受到自然选择和人工选择、重组、连锁不平衡、群体历史、突变率和近交水平等诸多因素的影响。近年来,随着高通量基因分型技术的使用以及二代测序成本的降低,畜禽育种已经进入基因组时代。对优秀种畜禽的选择强度大大提高,这在改善畜禽生产性能的同时不可避免地会造成动物的近交,从而导致近交衰退。根据ROH的分子信息能更准确地估计纯合性并可以检测过去和最近的近亲交配情况。基于ROH计算近交系数(FROH)反映的是个体的真实近交系数,即为实现的近交系数,而系谱近交系数FPED得到的是期望值。FROH在缺乏系谱信息的情况下,也可以用来推断一个群体的历史和近亲交配水平的信息。选择会改变优良畜禽的表型,并重塑了基因组不同区域的ROH模式。此外,选择增加了目标位点周围的纯合性,有害的变异被认为更频繁地出现在ROH区域,可以通过ROH检测,降低复杂疾病发生的风险。经过长期选择,品种内同群个体相同ROH在基因组中高频出现,产生ROH岛。研究证实了ROH和正在选择的基因组区域之间具有相关性。在实际应用中,可以通过生物信息的方法在ROH岛注释到ROH区域与经济性状相关的基因。此外,ROH也为评估畜禽遗传多样性提供了新的视角,对群体进行全基因组ROH检测,剖析每个群体的遗传结构,并利用FROH对当前育种计划中近交的影响进行评估,来调整育种方案,保护品种的遗传多样性。ROH已逐渐成为探究群体历史结构、评估近交水平、鉴定候选基因方面的重要指标。识别ROH主要有观察基因型计数法和基于模型分析两种方法。常用的检测软件有PLINK、GERMLINE、BEAGLE、GARLIC等。在实际应用中,PLINK是最常用的ROH检测工具。在畜禽中,由于牛的SNP芯片推出最早,因此最先开展ROH研究的是牛的群体,牛的ROH研究数量最多、最深入。目前,在猪、羊、鸡等畜禽中关于ROH的研究也逐渐增多。文章主要综述了ROH形成的原理和检测方法,以及在畜禽中的研究进展,以期为畜禽的遗传育种提供参考。