Combined approaches identify known and novel genes associated with sheep litter size and non‐seasonal breeding

Background There are abundant sheep breed resources in the Xinjiang region of China attributing to its diverse ecological system, which include several high-litter size sheep populations. Previous studies have confirmed that the major high prolificacy gene cannot be used to detect high litter size. Our research team found a resource group in Pishan County, southern Xinjiang. It showed high fertility with an average litter size of two to four in one birth, excellent breast development, and a high survival rate of lambs. In the present study, we used this resource as an ideal sample for studying the genetic mechanisms of high prolificacy in sheep. Methods Indigenous sheep populations from Xinjiang, with different litter sizes, were selected for the research, and specific-locus amplified fragment sequencing (SLAF-seq) technology was used to comprehensively screen single nucleotide polymorphisms (SNPs) from the whole genome that may cause differences in litter size. Novel genes associated with litter size of sheep were detected using genome-wide association studies (GWAS), providing new clues revealing the regulation mechanism of sheep fecundity. Candidate genes related to ovulation and litter size were selected for verification using Kompetitive Allele Specific polymerase chain reaction (KASP) cluster analysis. Results We identified 685,300 SNPs using the SLAF-seq technique for subsequent genome-wide analysis. Subsequently, 155 SNPs were detected at the genome-wide level. Fourteen genes related to sheep reproduction were notated: COIL, SLK, FSHR, Plxna3, Ddx24, CXCL12, Pla2g7, ATP5F1A, KERA, GUCY1A1, LOC101107541, LOC101107119, LOC101107809, and BRAF. Based on literature reports, 30 loci of seven genes and candidate genes (CXCL12, FSHR, SLK, GUCY1A1, COIL, LOC101107541, and LOC101107119) related to ovulation and litter size were selected for verification using KASP cluster analysis. Among them, nine loci of three genes were successfully genotyped. Three loci of FSHR (GenBank ID: 443299, g. 75320741G>A site), GUCY1A1 (GenBank ID: 101110000, g. 43266624C>T site), and COIL (GenBank ID: 101123134, g. 7321466C>G site) were found to be significantly or extremely significantly associated with litter size. These three loci are expected to be used as molecular markers to determine differences in litter size in sheep.

Peer Review #2 of "Identification of novel genes associated with litter size of indigenous sheep population in Xinjiang, China using specific-locus amplified fragment sequencing technology (v0.2)"

10.7287/peerj.8079v0.2/reviews/2 ◽

2019 ◽

Keyword(s):

Peer Review ◽

Litter Size ◽

Sequencing Technology ◽

Novel Genes ◽

Sheep Population ◽

Indigenous Sheep ◽

Specific Locus

Peer Review #1 of "Identification of novel genes associated with litter size of indigenous sheep population in Xinjiang, China using specific-locus amplified fragment sequencing technology (v0.1)"

10.7287/peerj.8079v0.1/reviews/1 ◽

2019 ◽

Keyword(s):

Peer Review ◽

Litter Size ◽

Sequencing Technology ◽

Novel Genes ◽

Sheep Population ◽

Indigenous Sheep ◽

Specific Locus

951: TOB1 and ID-1 Two Novel Genes Implicated in Bladder Cancer Progression and Prognosis

The Journal of Urology ◽

10.1016/s0022-5347(18)38188-6 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 252-252

Author(s):

Paul Perrotte ◽

Nadia Benachenou ◽

Pierre I. Karakiewicz ◽

Myriam Senay ◽

Fred Saad

Keyword(s):

Bladder Cancer ◽

Cancer Progression ◽

Novel Genes

Establishment of a genome-wide RNAi screen; Identification of novel genes involved in clonal maintenance of ALL

Klinische Pädiatrie ◽

10.1055/s-0034-1374830 ◽

2014 ◽

Vol 226 (03) ◽

Author(s):

F Ponthan ◽

D Pal ◽

J Vormoor ◽

O Heidenreich

Keyword(s):

Rnai Screen ◽

Novel Genes ◽

Genome Wide ◽

A Genome

Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size

Diabetologie und Stoffwechsel ◽

10.1055/s-0036-1580815 ◽

2016 ◽

Vol 11 (S 01) ◽

Author(s):

A Weingarten ◽

L Turchetti ◽

K Krohn ◽

M Kern ◽

I Klöting ◽

...

Keyword(s):

Body Fat ◽

Fat Mass ◽

Body Fat Mass ◽

Adipocyte Size ◽

Chromosome 10 ◽

Novel Genes

Pituitary and ovarian response to transient doe-litter separation in nursing rabbits

Reproduction ◽

10.1530/reprod/118.2.361 ◽

2000 ◽

pp. 361-366 ◽

Cited By ~ 8

Author(s):

E Ubilla ◽

PG Rebollar ◽

D Pazo ◽

AI Esquifino ◽

JM Alvarino

Keyword(s):

Pituitary Gland ◽

Litter Size ◽

Artificial Insemination ◽

Ovarian Response ◽

Major Effect ◽

Free Access ◽

Plasma Prolactin ◽

Follicular Waves ◽

Higher Sensitivity

The effects of a transient doe-litter separation on plasma prolactin, FSH and oestradiol concentrations, as well as the effect on LH response to exogenous GnRH administered at the time of artificial insemination, were determined in nursing rabbits. The effects on fertility, and litter size after parturition, as well as litter survival after doe-litter separation, were also studied. Control does (n = 12) had free access to nursing, whereas biostimulated does (n = 12) were separated from their litters for 48 h before artificial insemination. Plasma prolactin concentrations were decreased 24 h after the doe-litter separation (P < 0.05). The response of prolactin to suckling reached 10 times the basal values measured on day 10 after parturition (P < 0.0001). Increased oestradiol concentrations were found during the 48 h after the doe-litter separation: at 0 h, before artificial insemination (P< 0. 0001), 1.0-2.0 h after artificial insemination (P < 0.001), at 2.5 h (P < 0.05), 3.0 h (P < 0.01), and at 3.5 h (P < 0.05) after artificial insemination. Exogenous GnRH administered at the time of artificial insemination caused a greater LH response in does previously separated from their litters during 48 h (P < 0.01). The transient doe-litter separation did not affect plasma FSH concentrations, fertility, litter size or litter survival. These results suggest that a transient separation of nursing does from their litters before artificial insemination results in a decrease in plasma prolactin concentrations that could promote growth of follicular waves, and high steroidogenesis activity, leading to increased oestradiol concentrations and inducing higher sensitivity of the pituitary gland to exogenous GnRH. These findings associated to the absence of suckling episodes would lead to higher LH response and, therefore, exert a major effect on fertility.

Epigenetic Profiling Identifies Novel Genes for Ascending Aortic Aneurysm Formation with Bicuspid Aortic Valves

The Heart Surgery Forum ◽

10.1532/hsf.1247 ◽

2015 ◽

Vol 18 (4) ◽

pp. 134 ◽

Cited By ~ 12

Author(s):

Asad A Shah

Keyword(s):

Gene Expression ◽

Aortic Aneurysm ◽

Methylation Status ◽

Aortic Aneurysms ◽

Aortic Valves ◽

Ascending Aortic Aneurysm ◽

Novel Genes ◽

Aneurysm Formation ◽

Aortic Replacement ◽

Bicuspid Aortic Valves

Background: Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized. We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients.Methods: Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves. Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays. Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test. Results: Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10-4). The top gene was protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10-5) in bicuspid patients, as compared to tricuspid patients. Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including ACTA2 (4 probes, delta beta range: -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissectionsConclusions: Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms. The top gene was PTPN22, which is involved in T-cell receptor signaling and associated with various immune disorders. These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.