Genome-wide association study identifies loci and candidate genes for internal organ weights in Simmental beef cattle

An, Bingxing; Xia, Jiangwei; Chang, Tianpeng; Wang, Xiaoqiao; Miao, Jianyin; Xu, Lingyang; Zhang, Lupei; Gao, Xue; Chen, Yan; Li, Junya; Gao, Huijiang

doi:10.1152/physiolgenomics.00022.2018

Cited by 32 publications

(20 citation statements)

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“…In addition to the associations of both the SLIT2 variant and mRNA expression of SLIT2 and ROBO1 in basal plate of placenta with SPTB, SLIT2 mRNA levels in placentas were associated with the birth weight of fetuses born after spontaneous labor. A GWAS of beef cattle identified SLIT2 as a candidate gene that affects the weight of internal organs [46]. As the fetal growth and intrauterine distention negatively associates the duration of pregnancy [47] influence of SLIT2 on fetal size is a potential mechanism that remains to be studied as a cause of SPTB.…”

Section: Discussionmentioning

confidence: 99%

Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2

et al. 2019

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Spontaneous preterm birth (SPTB) is the leading cause of neonatal death and morbidity worldwide. Both maternal and fetal genetic factors likely contribute to SPTB. We performed a genome-wide association study (GWAS) on a population of Finnish origin that included 247 infants with SPTB (gestational age [GA] < 36 weeks) and 419 term controls (GA 38–41 weeks). The strongest signal came within the gene encoding slit guidance ligand 2 ( SLIT2 ; rs116461311, minor allele frequency 0.05, p = 1.6×10 −6 ). Pathway analysis revealed the top-ranking pathway was axon guidance, which includes SLIT2 . In 172 very preterm-born infants (GA <32 weeks), rs116461311 was clearly overrepresented (odds ratio 4.06, p = 1.55×10 −7 ). SLIT2 variants were associated with SPTB in another European population that comprised 260 very preterm infants and 9,630 controls. To gain functional insight, we used immunohistochemistry to visualize SLIT2 and its receptor ROBO1 in placentas from spontaneous preterm and term births. Both SLIT2 and ROBO1 were located in villous and decidual trophoblasts of embryonic origin. Based on qRT-PCR, the mRNA levels of SLIT2 and ROBO1 were higher in the basal plate of SPTB placentas compared to those from term or elective preterm deliveries. In addition, in spontaneous term and preterm births, placental SLIT2 expression was correlated with variations in fetal growth. Knockdown of ROBO1 in trophoblast-derived HTR8/SVneo cells by siRNA indicated that it regulate expression of several pregnancy-specific beta-1-glycoprotein ( PSG ) genes and genes involved in inflammation. Our results show that the fetal SLIT2 variant and both SLIT2 and ROBO1 expression in placenta and trophoblast cells may be correlated with susceptibility to SPTB. SLIT2-ROBO1 signaling was linked with regulation of genes involved in inflammation, PSG genes, decidualization and fetal growth. We propose that this receptor-ligand couple is a component of the signaling network that promotes SPTB.

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Section: Discussionmentioning

confidence: 99%

Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2

et al. 2019

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“…The signal on OAR6:38.1-39.6 Mb (S4 Fig and Table 4) was detected in Barbaresca and Laticauda and was previously reported as selection signature for fat-tail in these two breeds, also when compared with 13 Italian thin-tail breeds [9]. It includes the SLIT2 gene, a potential candidate for internal organ weights in Simmental beef cattle [32] and therefore possibly connected with fat deposition. This signal is worth investigating further, because it encompasses a large region (1.5 Mb) where the Barbaresca showed 27 SNP markers with allele frequency patterns that are highly differentiated from the Italian thin-tail breeds, 15 of which exceeded the significant threshold of Rsb P -value < 0.0001.…”

Section: Discussionmentioning

confidence: 56%

Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia

Mastrangelo¹,

Bahbahani²,

Moioli³

et al. 2018

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34Genomic regions subjected to selection frequently show signatures such as within-35 population reduced nucleotide diversity and outlier values of differentiation among differentially 36 selected populations. In this study, we analyzed 50K SNP genotype data of 373 animals belonging 37 to 23 sheep breeds of different geographic origins using the Rsb and F ST statistical approaches, to 38 identify loci associated with the fat-tail phenotype. We also checked if these putative selection 39 signatures overlapped with regions of high-homozygosity (ROH). The analyses identified novel 40 signals and confirmed the presence of selection signature in genomic regions that harbor candidate 41 genes known to affect fat deposition. Several genomic regions that frequently appeared in ROH 42 were also identified within each breed, but only two ROH islands overlapped with the putative 43 selection signatures. The results reported herein provide the most complete genome-wide study of 44 selection signatures for fat-tail in African and Eurasian sheep breeds; they also contribute insights 45 into the genetic basis for the fat tail phenotype in sheep, and confirm the great complexity of the 46 mechanisms that underlie quantitative traits, such as the fat-tail. 47 48 3 51been widely applied to livestock species to achieve more desirable/profitable phenotypes [1]. For 52 instance, sheep (Ovis aries) have been selected since domestication, approximately 9,000 years ago 53 [2]. This process of selection resulted in divergent sheep breeds, reared in different geographic 54 regions due to their different adaptability. Among these, fat-tail are an important class of sheep 55 breeds and represent about 25% of the world's sheep population [3] mainly distributed in the 56 Middle East, North and East Africa and Central Asia. According to Xu et al. [4] fat tails represent 57 the energy reserve necessary to survive critical conditions such as drought seasons and food 58 shortage. This statement being emphasized by Mwacharo et al. [5] who confirmed that the fat-tails 59 are the predominant sheep across the deserts of northern Africa, and in the highlands, semi-arid and 60 arid environments of eastern and southern Africa while the thin-tails occur in Sudan and in the sub-61 humid and humid regions of West Africa. 62The unique genetic patterns inscribed in the genome of individuals by natural and/or 63 artificial selection are defined as signatures of selection, which are usually regions of the genome 64 that harbor functionally important sequence variants [6]. Although human consumption of animal 65 fat has dramatically reduced in preference of leaner meat, the investigation of the potential 66 candidate genes involved in the fat-tail might contribute to exploring the genetics of fat deposition, 67 energy storage and adaptation to climate changes [7][8][9]. With the aim to identify candidate genes 68 with a potential role in these traits, several authors performed studies targeting the fat-tail 69 phenotype contrasted with the thi...

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“…The signal on OAR6:38.1–39.6 Mb was detected in Barbaresca and Laticauda and was previously reported as selection signature for fat-tail in these two breeds, also when compared with 13 Italian thin-tail breeds [9]. It includes the SLIT2 gene, a potential candidate for internal organ weights in Simmental beef cattle [32] and therefore possibly connected with fat deposition. This signal is worth investigating further, because it encompasses a large region (1.5 Mb) where the Barbaresca showed 27 SNP markers with allele frequency patterns that are highly differentiated from the Italian thin-tail breeds, 15 of which exceeded the significant threshold of Rsb P -value < 0.0001.…”

Section: Discussionmentioning

confidence: 69%

Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia

et al. 2019

View full text Add to dashboard Cite

Genomic regions subjected to selection frequently show signatures such as within-population reduced nucleotide diversity and outlier values of differentiation among differentially selected populations. In this study, we analyzed 50K SNP genotype data of 373 animals belonging to 23 sheep breeds of different geographic origins using the Rsb (extended haplotype homozygosity) and F ST statistical approaches, to identify loci associated with the fat-tail phenotype. We also checked if these putative selection signatures overlapped with regions of high-homozygosity (ROH). The analyses identified novel signals and confirmed the presence of selection signature in genomic regions that harbor candidate genes known to affect fat deposition. Several genomic regions that frequently appeared in ROH were also identified within each breed, but only two ROH islands overlapped with the putative selection signatures. The results reported herein provide the most complete genome-wide study of selection signatures for fat-tail in African and Eurasian sheep breeds; they also contribute insights into the genetic basis for the fat tail phenotype in sheep, and confirm the great complexity of the mechanisms that underlie quantitative traits, such as the fat-tail.

show abstract

Genome-wide association study identifies loci and candidate genes for internal organ weights in Simmental beef cattle

Cited by 32 publications

References 63 publications

Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2

Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2

Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia

Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia

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