New genomic features of the polled intersex syndrome variant in goats unraveled by long‐read whole‐genome sequencing

Simon, Rebecca; Lischer, Heidi E. L.; Pieńkowska-Schelling, Aldona; Keller, Irene; Häfliger, Irene M.; Letko, Anna; Schelling, C.; Lühken, Gesine; Drögemüller, Cord

doi:10.1111/age.12918

Cited by 16 publications

(18 citation statements)

References 41 publications

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“…Our GWAS and fine-mapping results were consistent with the two recent research results from Switzerland and China that used long-read whole-genome sequencing of two genetically female goats (a PIS-affected and a horned control) and whole-genome selective sweep of intersex goats from China, respectively [15,16] . Although the results of the three groups are consistent, our study is different from the other two studies.…”

Section: Discussionsupporting

confidence: 89%

“…A 1.8 kb insertion in the 3' untranslated region (3' UTR) of RXFP2 has been identified to be associated with the horn/polledness of sheep [13] ; RXFP2 pseudogenization has been identified in Moschidae and Hydropotinae [12] , and a 212 bp insertion near gene OLIG1 (~65 kb away) was found to produce hornless cattle [14] . Recently, two groups reported that a novel intersexuality-associated variant consisting of ∼0.48 Mb duplicated fragment (including ERG and KCNJ15) downstream of the ∼20 Mb PIS region was reversely inserted into the PIS locus of goat [15,16] . However, the development of polledness trait in goats is very special because it is closely related to intersexuality, which increases the difficulties in the identification of hornless-related genes.…”

Section: / 22mentioning

confidence: 99%

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Fine mapping of goat polledness variant in six Chinese native breeds

Chen

Yang

et al. 2021

Preprint

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Background: The genetic mechanism of goat polledness has been studied for decades, but identifying causative variants and functional genes remains challenging. Results: Using a genome-wide association study (GWAS), we identified a significant striking locus for polledness in two different goat breeds. To reduce the linkage disequilibrium among variants for localizing causative variants in the finer region, we sequenced 79 goats from six Chinese native breeds (Jining Gray, Matou, Guizhou black, Yunnan black bone, Chaidamu, and Ujumqin) and identified 483.5 kb CNV (150,334,567-150,818,099) translocated into the previously identified 11.7 kb polled intersex syndrome region, which was consistent with previous research using intersex goat populations. Within the 483.5 kb CNV, a ~322 bp horn-specific element, similar to the superfamily of tRNA-derived families of SINEs, located at the first intron of the ERG gene was identified. The results of the GO enrichment analysis showed that the Horn-SINE element-associated genes were involved in both nervous system and head development. Finally, we used RNA sequencing to investigate gene expression profiles in the horn bud and skin tissues of horned and polled goats. We identified 1077 and 1222 differentially expressed genes between the horn bud and skin tissue in polled and horned goats, respectively. We also identified 367 differentially expressed genes in horn buds between polled and horned animals and found that the two CNV-related genes, ERG and FOXL2 were upregulated in the horn bud of polled goats. Gene functional enrichment analysis demonstrated that the downregulated genes in the horn bud of polled goats were enriched in skeletal system development, whereas the upregulated genes were significantly overexpressed in muscle tissue development.

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Section: Discussionsupporting

confidence: 89%

Section: / 22mentioning

confidence: 99%

Fine mapping of goat polledness variant in six Chinese native breeds

Chen

Yang

et al. 2021

Preprint

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“…This syndrome is a disorder of sexual development showing an association with the polled phenotype and intersexuality. PIS is caused by a 10-kb deletion and a 480-kb insertion containing the genes ERG and KCNJ15 leading to a complex rearrangement ( Simon et al, 2020 ). In cattle, polledness is caused by complex duplication variants on BTA1 that leads to differences in gene expression ( Wiedemar and Drögemüller, 2015 ).…”

Section: Common Trait Selection Affects Similar Genes Across Livestock Speciesmentioning

confidence: 99%

Review: Balancing Selection for Deleterious Alleles in Livestock

Derks

Steensma

2021

Front. Genet.

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Harmful alleles can be under balancing selection due to an interplay of artificial selection for the variant in heterozygotes and purifying selection against the variant in homozygotes. These pleiotropic variants can remain at moderate to high frequency expressing an advantage for favorable traits in heterozygotes, while harmful in homozygotes. The impact on the population and selection strength depends on the consequence of the variant both in heterozygotes and homozygotes. The deleterious phenotype expressed in homozygotes can range from early lethality to a slightly lower fitness in the population. In this review, we explore a range of causative variants under balancing selection including loss-of-function variation (i.e., frameshift, stop-gained variants) and regulatory variation (affecting gene expression). We report that harmful alleles often affect orthologous genes in different species, often influencing analogous traits. The recent discoveries are mainly driven by the increasing genomic and phenotypic resources in livestock populations. However, the low frequency and sometimes subtle effects in homozygotes prevent accurate mapping of such pleiotropic variants, which requires novel strategies to discover. After discovery, the selection strategy for deleterious variants under balancing selection is under debate, as variants can contribute to the heterosis effect in crossbred animals in various livestock species, compensating for the loss in purebred animals. Nevertheless, gene-assisted selection is a useful tool to decrease the frequency of the harmful allele in the population, if desired. Together, this review marks various deleterious variants under balancing selection and describing the functional consequences at the molecular, phenotypic, and population level, providing a resource for further study.

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“…Although PIS has been localized by predecessors, in recent studies, different versions of PIS sites have been discovered (Kijas et al., 2013; Simon et al., 2020). Therefore, the complex mechanism of sex reversal caused by PIS is currently unclear, and there are few studies on the gene expression levels of intersex goats.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of gene expression in normal goat ovary and intersex goat gonad

Yang

Han

Jun

et al. 2020

Reprod Domestic Animals

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Intersexuality is a congenital reproductive disorder that usually occurs in hornless goats, hindering breeding of goats with hornless traits and the development of the goat industry. In this study, we aimed to identify differentially expressed genes in intersex and normal goat gonads by comparing gene transcription profiles of intersex and normal goat gonads. As intersex goats are genetically based on females, we chose female goats as controls. The goats in the control group and the experimental group were both over one‐year old. We evaluated the anatomical characteristics of the reproductive organs of five intersex goats using histopathological methods. The gonads were found to be ovarian and testicular types. RNA‐Seq technology was used to identify differentially expressed genes in gonads and normal goat ovary tissues. Transcription analysis results were verified by qPCR. The results showed that 2,748 DEGs were upregulated and 3,327 DEGs were downregulated in intersex ovaries unlike in controls, whereas 2006 DEGs were upregulated and 2032 DEGs were downregulated in the interstitial testes. Many of these genes play important roles in mammalian sex determination and sex differentiation, such as SOX9, WT1, GATA4, DMRT1, DHH, AMH, CYP19A1 and FST. We found that many DEGs are involved in biological developmental regulation by GO and KEGG enrichment analyses, and that most genes associated with the steroid synthesis pathway were downregulated. The DEGs identified in this study may be involved in the regulation of intersex goat sex determination and differentiation, and may increase our understanding of the molecular mechanisms of mammalian sex differentiation.

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New genomic features of the polled intersex syndrome variant in goats unraveled by long‐read whole‐genome sequencing

Cited by 16 publications

References 41 publications

Fine mapping of goat polledness variant in six Chinese native breeds

Fine mapping of goat polledness variant in six Chinese native breeds

Review: Balancing Selection for Deleterious Alleles in Livestock

Transcriptomic analysis of gene expression in normal goat ovary and intersex goat gonad

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