Biology subjects

Salas, D.

Publications and source records attributed to Salas, D..

4 recordsLinked to original sources

bioRxiv2026

DNA end-resection is stimulated by an interaction between BRCA1 exon 11 and TOPBP1

Approximately 60% of the tumour suppressor protein BRCA1 is encoded by a single exon. Many tumours carry mutations in this exon, often resulting in exon skipping and thus a protein of a severely reduced size. Although none of the well-described protein domains of BRCA1 are encoded by this exon 11, the isoform lacking this part shows a hypomorphic activity in homologous recombination. To better understand the function of this large exon, we performed proteomic analyses to identify interaction partners via this part of the protein. Here, we report a DNA damage-and phospho-dependent interaction of TOPBP1 to the protein region of BRCA1 encoded by exon 11. Mechanistically, this interaction is required for BRCA1s role in end-resection during homologous recombination. In contrast, the interaction is not required for TOPBP1s role in ATR activation. Our data provide novel mechanistic insight into the function of this poorly characterized part of the BRCA1 protein.

molecular biology↗

bioRxiv2019

High-throughput single nucleotide polymorphism (SNP) discovery and validation through whole-genome resequencing of hundreds of individuals in Nile tilapia (Oreochromis niloticus)

Nile Tilapia (Oreochromis niloticus) is the second most important farmed fish in the world and a sustainable source of protein for human consumption. Several genetic improvement programs have been established for this species in the world and so far, they are mainly based on conventional selection using genealogical and phenotypic information to estimate the genetic merit of breeders and make selection decisions. Genome-wide information can be exploited to efficiently incorporate traits that are difficult to measure in the breeding goal. Thus, SNPs are required to investigate phenotype-genotype associations and determine the genomic basis of economically important traits. We performed de novo SNP discovery in three different populations of farmed tilapias. A total of 29.9 million non-redundant SNPs were identified through Illumina (HiSeq 2500) whole-genome resequencing of 326 individual samples. After applying several filtering steps including removing SNP based on genotype and site quality, presence of Mendelian errors, and non unique position in the genome, a total of high quality 50,000 SNP were selected for validation purposes. These SNPs were highly informative in the three populations analyzed showing between 43,869 (94%) and 46,139 (99%) SNP in HWE; 37,843 (76%) and 45,171(90%) SNP with a MAF higher than 0.05 and; 43,450 (87%) and 46,570 (93%) SNPs with a MAF higher than 0.01. The final list of 50K SNPs will be very useful for the dissection of economically relevant traits, enhancing breeding programs through genomic selection as well as supporting genetic studies in farmed populations Nile tilapia using dense genome-wide information.

genomics↗

bioRxiv2019

Fine mapping using whole-genome sequencing confirms anti Mullerian hormone as a major gene for sex determination in farmed Nile tilapia (Oreochromis niloticus L.)

Nile tilapia (Oreochromis niloticus) is one of the most cultivated and economically important species in world aquaculture. Faster male development during grow-out phase is considered a major problem that generate heterogeneous sizes of fish at harvest. Identifying genomic regions associated with sex determination in Nile tilapia is a research topic of great interest. The objective of this study was to identify genomic variants associated with sex determination in three commercial populations of Nile tilapia. Whole-genome sequencing of 326 individuals was performed, and a total of 2.4 million high-quality bi-allelic single nucleotide polymorphisms (SNPs) were identified. A genome-wide association study (GWAS) was conducted to identify markers associated with the binary sexual trait (males = 0; females = 1). A mixed logistic regression GWAS model was fitted and a genome-wide significant signal comprising 36 SNPs, located on chromosome 23 spanning a genomic region of 536 kb, was identified. Ten out of these 36 genetic variants, intercept the anti-Mullerian hormone gene. Other significant SNPs were located in the neighboring Amh gene region. This gene has been strongly associated with sex determination in several vertebrate species, playing an essential role in the differentiation of male and female reproductive tissue in early stages of development. This finding provides useful information to better understand the genetic mechanisms underlying sex determination in Nile tilapia.

genomics↗

bioRxiv2019

Genome-wide association study and low-cost genomic predictions for growth and fillet yield in Nile tilapia (Oreochromis niloticus)

Fillet yield (FY) and harvest weight (HW) are economically important traits in Nile tilapia production. Genetic improvement of these traits, especially for FY, are lacking, due to the absence of efficient methods to measure the traits without sacrificing fish and the use of information from relatives to selection. However, genomic information could be used by genomic selection to improve traits that are difficult to measure directly in selection candidates, as in the case of FY. The objectives of this study were: (i) to perform genome-wide association studies (GWAS) to dissect the genetic architecture of FY and HW, (ii) to evaluate the accuracy of genotype imputation and (iii) to assess the accuracy of genomic selection using true and imputed low-density (LD) single nucleotide polymorphism (SNP) panels to determine a cost-effective strategy for practical implementation of genomic information in tilapia breeding programs. The data set consisted of 5,866 phenotyped animals and 1,238 genotyped animals (108 parents and 1,130 offspring) using a 50K SNP panel. The GWAS were performed using all genotyped and phenotyped animals. The genotyped imputation was performed from LD panels (LD0.5K, LD1K and LD3K) to high-density panel (HD), using information from parents and 20% of offspring in the reference set and the remaining 80% in the validation set. In addition, we tested the accuracy of genomic selection using true and imputed genotypes comparing the accuracy obtained from pedigree-based best linear unbiased prediction (PBLUP) and genomic predictions. The results from GWAS supports evidence of the polygenic nature of FY and HW. The accuracy of imputation ranged from 0.90 to 0.98 for LD0.5K and LD3K, respectively. The accuracy of genomic prediction outperformed the estimated breeding value from PBLUP. The use of imputation for genomic selection resulted in an increased relative accuracy independent of the trait and LD panel analyzed. The present results suggest that genotype imputation could be a cost-effective strategy for genomic selection in tilapia breeding programs.

genomics↗