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. 2018 Apr 10:9:118.
doi: 10.3389/fgene.2018.00118. eCollection 2018.

Genome-Wide Association Analyses Highlight the Potential for Different Genetic Mechanisms for Litter Size Among Sheep Breeds

Song-Song Xu  1   2 , Lei Gao  3   4 , Xing-Long Xie  1   2 , Yan-Ling Ren  5 , Zhi-Qiang Shen  5 , Feng Wang  6 , Min Shen  3   4 , Emma Eyϸórsdóttir  7 , Jón H Hallsson  7 , Tatyana Kiseleva  8 , Juha Kantanen  9 , Meng-Hua Li  1   2
Affiliations

Genome-Wide Association Analyses Highlight the Potential for Different Genetic Mechanisms for Litter Size Among Sheep Breeds

Song-Song Xu et al. Front Genet. .

Abstract

Reproduction is an important trait in sheep breeding as well as in other livestock. However, despite its importance the genetic mechanisms of litter size in domestic sheep (Ovis aries) are still poorly understood. To explore genetic mechanisms underlying the variation in litter size, we conducted multiple independent genome-wide association studies in five sheep breeds of high prolificacy (Wadi, Hu, Icelandic, Finnsheep, and Romanov) and one low prolificacy (Texel) using the Ovine Infinium HD BeadChip, respectively. We identified different sets of candidate genes associated with litter size in different breeds: BMPR1B, FBN1, and MMP2 in Wadi; GRIA2, SMAD1, and CTNNB1 in Hu; NCOA1 in Icelandic; INHBB, NF1, FLT1, PTGS2, and PLCB3 in Finnsheep; ESR2 in Romanov and ESR1, GHR, ETS1, MMP15, FLI1, and SPP1 in Texel. Further annotation of genes and bioinformatics analyses revealed that different biological pathways could be involved in the variation in litter size of females: hormone secretion (FSH and LH) in Wadi and Hu, placenta and embryonic lethality in Icelandic, folliculogenesis and LH signaling in Finnsheep, ovulation and preovulatory follicle maturation in Romanov, and estrogen and follicular growth in Texel. Taken together, our results provide new insights into the genetic mechanisms underlying the prolificacy trait in sheep and other mammals, suggesting targets for selection where the aim is to increase prolificacy in breeding projects.

Keywords: biological pathways; genome-wide association study; prolificacy; regulation; sheep.

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Figures

FIGURE 1
FIGURE 1
(A) Geographic locations for five sheep breeds of high (WAD, Wadi sheep; HUS, Hu sheep; ICE, Icelandic sheep; FIN, Finnsheep; and ROM, Romanov sheep) and one low (TEX, Texel sheep) prolificacy. (B) Neighbor-joining tree of the six sheep breeds with 1000 bootstrap replicates.
FIGURE 2
FIGURE 2
Phenotypic distribution of litter size in the six sheep breeds (WAD, Wadi sheep; HUS, Hu sheep; ICE, Icelandic sheep; FIN, Finnsheep; ROM, Romanov sheep; and TEX, Texel sheep).
FIGURE 3
FIGURE 3
Manhattan plots of GWAS are shown on (A) Wadi, (B) Hu, (C) Icelandic, (D) Finnsheep, (E) Romanov and (F) Texel sheep. The 5% genome-wide significant threshold value is indicated by a dotted line. The significant SNPs surrounding the genes previously reported to be associated with reproduction are annotated at the chromosome-wise and genome-wide 5% significance after the Bonferroni correction.
FIGURE 4
FIGURE 4
Plots of regional association results for the top significant SNP (red square) and their near SNPs in (A) Wadi, (B) Hu, (C) Icelandic, (D) Finnsheep, (E) Romanov, and (F) Texel sheep. Different colors represent the r2 values of pair-wise LD estimates.
FIGURE 5
FIGURE 5
Genotypic distributions of the top significant SNPs for the litter size (LS) phenotype in (A) Wadi, (B) Hu, (C) Icelandic, (D) Finnsheep, (E) Romanov, and (F) Texel sheep, respectively. The means LS were calculated for various breeds. Number of ewes per group of genotype is mentioned. Pairwise statistical comparisons between means of genotype’s clades were performed using Student’s t-test. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
FIGURE 6
FIGURE 6
Gene ontology (GO) enrichments based on the functional genes surrounding the significant SNPs at the chromosome-wise 5% level.
FIGURE 7
FIGURE 7
Protein–protein interaction networks identified by using STRING database. Each line indicated known signaling pathways and protein complexes.
FIGURE 8
FIGURE 8
Heatmap of the candidate genes identified from six sheep breeds (WAD, Wadi sheep; HUS, Hu sheep; ICE, Icelandic sheep, FIN, Finnsheep, ROM, Romanov sheep, and TEX, Texel sheep) enriched for expression in different ewes tissues deposited in the EBI Gene Expression Atlas database. The FPKM (fragments per kilobase of transcript per million mapped reads) value is used to measure the expression level.
FIGURE 9
FIGURE 9
Follicle growth and ovulation process for the role of the candidate genes identified from six sheep breeds in litter size.
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References

    1. Aulchenko Y. S., Ripke S., Isaacs A., van Duijn C. M. (2007). GenABEL: an R library for genome-wide association analysis. Bioinformatics 23 1294–1296. 10.1093/bioinformatics/btm108 - DOI - PubMed
    1. Bachelot A., Monget P., Imbert-Bollore P., Coshigano K., Kopchick J. J., Kelly P. A., et al. (2002). Growth hormone is required for ovarian follicular growth. Endocrinology 143 4104–4112. 10.1210/en.2002-220087 - DOI - PubMed
    1. Baird D. T., Cnattingius S., Collins J., Evers J. L. H., Glasier A., Heitmann B. L., et al. (2006). Nutrition and reproduction in women. Hum. Reprod. Update 12 193–207. 10.1093/humupd/dmk003 - DOI - PubMed
    1. Basini G., Bussolati S., Baioni L., Grasselli F. (2011). Gelatinases (MMP2 and MMP9) in swine antral follicle. Biofactors 37 117–120. 10.1002/biof.153 - DOI - PubMed
    1. Ben Sassi N., Gonzalez-Recio O., de Paz-del Rio R., Rodriguez-Ramilo S. T., Fernandez A. I. (2016). Associated effects of copy number variants on economically important traits in Spanish Holstein dairy cattle. J. Dairy Sci. 99 6371–6380. 10.3168/jds.2015-10487 - DOI - PubMed