Lead to abnormalities suggestive of hypothalamic dysfunction similar to the report of a distinct fluorescence pattern on Hep-2000TM cells

Indicine breeds, such as Nellore cattle, form the majority of the beef herds in tropical and subtropical countries. Zebus generally take longer to reach puberty than taurines, making the improvement of reproductive performance an impending challenge in the production systems of these regions of the world. Scrotal circumference evaluated at yearling is the most recorded reproductive trait in breeding programs for beef cattle, as the trait is inexpensive and easy to measure, is highly heritable, and is associated with testis development, quantitative and qualitative semen parameters, age at puberty in bulls and related heifers, heifer pregnancy, and body weight. Consequently, SC is used in these programs as a major indicator of precocity and fertility. Characterizing genomic regions that explain differences in SC in B. indicus can contribute to the identification of reproductive performance informative molecular markers to assist breeding, as well as to the mapping of loci implicated in reproductive biology. In this paper, we analyzed data of estimated breeding values from 861 Nellore bulls genotyped for over 777,000 single nucleotide polymorphism markers. We aimed at identifying putative genomic regions explaining differences in SC in B. indicus cattle via genome-wide mapping. The genome-wide mapping analysis detected positional candidate loci explaining approximately 4% of the dEBVs for SC. Although this represents only a fraction of the trait variance, this percentage is substantial considering that 180 loci associated with human adult height, a highly heritable and classic polygenic trait, explain only 10% of the phenotypic variance together. This is evidence that multiple loci across the genome are involved in the LEE011 abmole complex inheritance of SC, and the functional candidate genes filtered here may only scratch the surface of the molecular mechanisms underlying the trait. The dissection of the pathways regulating precocity in B. indicus cattle will require multiple studies across breeds and trait models, with intensive multidisciplinary reasoning. Nevertheless, the loci reported here excel from the genome background, and represent important data in the context of bovine reproductive biology. The region explaining the largest proportion of SC variance in the present study mapped to the beginning of chromosome 21, peaking around 1.5 Mb. The closest gene found in this region was MAGEL2. The orthologous human and murine genes regulate normal circadian output, and are highly expressed in the suprachiasmatic nucleus of the hypothalamus. The human MAGEL2 has been implicated in Prader-Willi Syndrome, a genetic disorder characterized by short stature, low muscle tone, cognitive disabilities, increased food intake, obesity, low levels of insulin and insulin-like growth factor 1, incomplete sexual development, hypogonadism, and male infertility. The disorder manifests when a segment on human chromosome 15, which encompasses seven maternally imprinted genes including MAGEL2, presents a deletion or loss of expression of the paternal alleles.

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