基于全基因组重测序的山羊产羔数性状关键调控基因的筛选

doi:10.3864/j.issn.0578-1752.2022.23.015

Abstract

Abstract:

【Objective】 The purpose of this study was to analyze the genome of different fecundity populations of goats (Capra hircus) and to explore the key regulatory genes involved in the regulation of litter size traits of Chuanzhong black goats (CBGs), and to provide the theoretical reference for analyzing the genetic mechanism of litter size traits and molecular genetic improvement of fecundity in goats. 【Method】 The high fecundity (HF) CBG does (n = 6) that produced 4-6 kids per doe kidding and low fecundity (LF) does (n = 6) that produced only one kid per doe kidding were chosen in this study. The jugular blood samples were collected to extract genomic DNA. The 350 bp double-terminal sequencing library was constructed, and then 12 whole genome libraries were resequenced by IlluminaHiSeqPE150 platform. The clean data from sequencing were mapped to goat reference genome ARS1 by using BWA software, and two whole-genome scanning analysis methods (Fst and Hp) were used to comprehensively analyze the high-quality SNPs obtained to identify candidate regions. GO analysis and KEGG pathway analysis were performed on the G:Profiler and KOBAS online databases, respectively, to screen candidate genes for regulating the number of kids in CBGs. To further identify the key genetic markers that regulate the number of kids, the synonymous and non-synonymous single nucleotide polymorphisms (SNPs) of reproductive candidate genes were mapped and screened according to the variation analysis report of genome resequencing. The amplified products of 12 goat samples were sequenced by Sanger sequencing to verify the resequencing results.【Result】 A total of 431.50 Gb clean data were obtained from the genome resequencing study of 12 CBGs. Through mutation detection and annotation, 7 771 417 SNPs were detected in HF group and 8 935 907 SNPs were detected in LF group, and all types of the LF group SNPs were more than those in HF group. The windows that reach the maximum ZFst value of top 5% and the minimum ZHp value of top 5% were set as candidate regions. A total of 130 strong selection signals were annotated in the regions with low heterozygosity and high genetic differentiation, of which 84, 59 and 13 genes were annotated in HF group, LF group and shared window, respectively. GO enrichment analysis and KEGG pathway showed that 19 candidate genes were involved in the regulation of reproduction, reproduction and embryonic development of CBG, including 11 HF group-specific candidate genes (ADCY10, DRD1, HS6ST1, IGFBP7, MSX2, NOG, NPHP4, PAPPA, PRLHR, TDRP, and XYLT1), and five strong selection signal genes (ANXA5, IGF1, EDNRA, FANCL, and TAC1) in LF group, and three window genes (AKR1B3, HDAC4 and OPRM1) in HF group shared with LF group. The most GO terms, such as G-protein-coupled receptor activity, hormone response and neuropeptide signal pathway, contained these 19 candidate genes. In addition, nine of the 14 HF candidate genes were significantly enriched in metabolic pathway, neuroactive ligand-receptor interaction, glycosaminoglycan-heparan sulfate/heparin biosynthesis, calcium signal pathway, cAMP signal pathway and folate biosynthesis KEGG pathways (P<0.05). Among the 19 reproductive candidate genes, there were two synonymous mutations (MSX2 G771T, ADCY10 A4662G) and two non-synonymous mutations (PRLHR G529, DRD1 A281T), which were only located in the HF candidate genes. The Sanger sequencing showed that polymorphisms of MSX2, PRLHR and DRD1 gene mutations could be detected, and this result was consistent with the results of genome resequencing, in which PRLHR G529A polymorphism led to alanine mutation to threonine, and DRD1 A281T polymorphism led to early termination of translation.【Conclusion】 A total of 11 HF group-specific candidate genes were found in this study, which were speculated to be the key regulatory genes for fecundity trait. The mutations of PRLHR gene exon G529A and DRD1 exon A281T might be the key genetic markers for regulating prolificacy traits in goats, which had great application value in improving reproductive performance of goats.

Key words: Chuanzhong black goat, genome resequencing, fecundity, candidate genes

LI Heng,ZI XiangDong,WANG Hui,XIONG Yan,LÜ MingJie,LIU Yu,JIANG XuDong. Screening of Key Regulatory Genes for Litter Size Trait Based on Whole Genome Re-Sequencing in Goats (Capra hircus)[J].Scientia Agricultura Sinica, 2022, 55(23): 4753-4768.

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山羊编号 Symbol	胎产羔数（只） Litter size
山羊编号 Symbol	头胎First birth	二胎Second pregnancy
HF1	4	5
HF2	4	4
HF3	5	4
HF4	4	6
HF5	5	4
HF6	4	4
LF1	1	1
LF2	1	1
LF3	1	1
LF4	1	1
LF5	1	1
LF6	1	1

位点Locus	引物序列Primer sequence (5′→3′)	产物大小Product size（bp）	退火温度Tm (℃)
PRLHR（G529A）	F: GGCGTAGGAGGGGTTGGATA	1524	59.8
PRLHR（G529A）	R: CAACCCCAACCAGCCATTT
DRD1（A281T）	F:ACCGCATCCATCCTCAACCT	473	60.0
DRD1（A281T）	R: ATCACCGACAGAGTCTTCAG
MSX2（G770T）	F：GCAAAACCTATGCTGCCCTC	350	60.0
MSX2（G770T）	R：GGCTTGGGTGTCTCCAGTCA
ADCY10（A4662G）	F：CTACCCAAGGCTTTACCATC	242	60.0
ADCY10（A4662G）	R：CCACACCCAGTGAAATCCAA

项目 Category	SNPs数 Number of SNPs
项目 Category	低繁组LF	高繁组HF
基因上游1 kb区域Upstream	50798	44949
使基因获得终止密码子的变异Stop gain	323	300
使基因失去终止密码子的变异Stop loss	39	31
同义变异Synonymous	35520	31260
非同义变异Non-synonymous	24706	21834
变异位于内含子区域Intronic	2473891	2145836
变异位于剪接位点Splicing	237	214
基因下游1 kb区域Downstream	50349	44201
基因上游1 kb区域/基因下游1 kb区域Upstream/downstream	828	720
变异位于基因间区Intergenic	6262768	5450243
变异位于5’ UTR UTR5	16072	14378
变异位于3’ UTR UTR3	20376	17451
转换Transitions	6290461	5466615
颠换Transversions	2645446	2304802
转换与颠换的比率 Transitions/Transversions	2.377	2.371
SNP总个数Total SNP	8935907	7771417

GO条目 GO Term	GO分类号 GO ID	矫正P值 Corrected P-value	基因名 Symbols
繁殖过程 Reproductive process	GO:0022414	2.02563E-05	ADCY10、AKR1B3、DRD1、HDAC4、HS6ST1、IGFBP7、MSX2、NOG、NPHP4、OPRM1、PAPPA、PRLHR、TDRP、ANXA5、EDNRA、FANCL、IGF1、SPINK1、TAC1
繁殖 Reproduction	GO:0000003	2.04405E-05	ADCY10、AKR1B3、DRD1、HDAC4、HS6ST1、IGFBP7、MSX2、NOG、NPHP4、OPRM1、PAPPA、PRLHR、TDRP、ANXA5、EDNRA、FANCL、IGF1、SPINK1、TAC1
胚胎发育Embryo development	GO:0009790	0.003942756	EDNRA、HS6ST1、IGF1、MSX2、NOG、TDGF1、XYLT1
生殖过程调控 Regulation of reproductive process	GO:2000241	0.009505443	HDAC4、MSX2、ANXA5、IGF1、SPINK1、TAC1

Screening of Key Regulatory Genes for Litter Size Trait Based on Whole Genome Re-Sequencing in Goats (Capra hircus)

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