Tracing selection signatures in the pig genome gives evidence for selective pressures on a unique curly hair phenotype in Mangalitza

Selection for desirable traits and breed-specific phenotypes has left distinctive footprints in the genome of pigs. As representative of a breed with strong selective traces aiming for robustness, health and performance, the Mangalitza pig, a native curly-haired pig breed from Hungary, was investigated in this study. Whole genome sequencing and SNP chip genotyping was performed to detect runs of homozygosity (ROH) in Mangalitza and Mangalitza-crossbreeds. We identified breed specific ROH regions harboring genes associated with the development of the curly hair type and further characteristics of this breed. Further analysis of two matings of Mangalitza with straight-coated pig breeds confirmed an autosomal dominant inheritance of curly hair. Subsequent scanning of the genome for variant effects on this trait revealed two variants potentially affecting hair follicle development and differentiation. Validation in a large sample set as well as in imputed SNP data confirmed these variants to be Mangalitza-specific. Herein, we demonstrated how strong artificial selection has shaped the genome in Mangalitza pigs and left traces in the form of selection signatures. This knowledge on genomic variation promoting unique phenotypes like curly hair provides an important resource for futures studies unraveling genetic effects for special characteristics in livestock

SNP detection and prediction of variability between chicken lines using genome resequencing of DNA pools

<p>Abstract</p> <p>Background</p> <p>Next-generation sequencing technologies are widely used for detection of millions of Single Nucleotide Polymorphisms (SNPs) and also provide a means of assessing their variation. This information is useful for composing subsets of highly informative SNPs for region-specific or genome-wide analysis and to identify mutations regulating phenotypic differences within or between populations. In this study, we investigated the sensitivity of SNP detection and introduced the flanking SNPs value (FSV) as a novel measure for predicting SNP-variability using ~5X genome resequencing with ABI SOLID and DNA pools from two chicken lines divergently selected for juvenile bodyweight.</p> <p>Results</p> <p>Genotyping with a 60 K SNP chip revealed polymorphisms within or between two divergently selected chicken lines for 31 363 SNPs, 48% of which were also detected using resequencing of DNA pools. SNP detection using resequencing was more powerful for positions with larger differences in allele frequency between the lines. About 50% of the SNPs with non-reference allele frequencies in the range 0.5-0.6 and 67% of those with frequencies > 0.9 could be detected. On average, ~3.7 SNPs/kb were detected by resequencing, with about 5% lower density on microchromosomes than on macrochromosomes. There was a positive correlation between the observed between-line SNP variation from the 60 K chip analysis and our proposed FSV score computed from the genome resequencing data. The strongest correlations on macrochromosomes and microchromosomes were observed when the FSV was calculated with total flanking regions of 62 kb (correlation 0.55) and 38 kb (correlation 0.45), respectively.</p> <p>Conclusions</p> <p>Genome resequencing with limited coverage (~5X) using pooled DNA samples and three non-reference reads as a threshold for SNP detection, identified 50 - 67% of the 60 K SNPs with a non-reference allele frequency larger than 0.5. The SNP density was around 5% lower on the microchromosomes, most likely because of their higher gene content. Our proposed method to estimate the SNP variation (FSV) uses additional sequence information to better predict SNP informativity. The FSV scores showed higher correlations for SNPs with a larger difference in allele frequency between the populations. The correlation was strongest on macrochromosomes, probably due to a lower recombination rate.</p

TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis

Background: TAR DNA binding protein, encoded by TARDBP, was shown to be a central component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). Recently, mutations in TARDBP have been linked to familial and sporadic ALS. Methodology/Principal Findings: To further examine the frequency of mutations in TARDBP in sporadic ALS, 279 ALS cases and 806 neurologically normal control individuals of European descent were screened for sequence variants, copy number variants, genetic and haplotype association with disease. An additional 173 African samples from the Human Gene Diversity Panel were sequenced as this population had the highest likelihood of finding changes. No mutations were found in the ALS cases. Several genetic variants were identified in controls, which were considered as non-pathogenic changes. Furthermore, pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus

Genomic Adaptation of Local Cattle Breeds in the Alpine Massif

Understanding adaptive ability of livestock is a key factor in the context of global climate change and become a crucial focus in conservation and management for a sustainable farming in a changing environment. One way to better understand adaptation abilities is to identify genes underlying adaptation phenotypes. This goal can be achieved by genetically characterising livestock species and detecting footprints of selection in the animal genome. The recent availability of genome-wide SNP panels allows providing background information concerning genome structure in domestic animals, opening new perspectives to livestock genetics. In order to investigate the genetic regions with a potential adaptive role, we investigate 24 cattle breeds, (high productive specialised breeds and several autochthonous populations) reared in six different neighbouring nations from East to West Alpine Massif. Several analyses have been performed to detect footprints of selection and genomic regions associated with climate variables. More precisely, using breed GPS coordinates, 4 climatic variables (annual mean temperature, annual precipitation, annual mean radiation, and annual mean moisture index) were extracted from the Climond database. In order to identify footprints of selection, a whole genome scan for adaptive differentiation were performed using Bovine 50K SNP chip genotyping data with the XtX model implemented in the BAYPASS software. In addition, across-population whole genome scans for association with the population-specific climatic variables were performed using the AUX model. Footprints of selection were detected on BTA6 and BTA18 pointing out several candidate genes (i.e. LCORL, PDGFRA, KDR and SPG7); moreover different genomic regions (on BTA 6, 10, 19 and 20) were associated with annual mean radiation. Ongoing analyses will specify candidate regions and genes involved in local adaptation in the Alpine massif

Whole-genome analysis of introgressive hybridization and characterization of the bovine legacy of Mongolian yaks

The yak is remarkable for its adaptation to high altitude and occupies a central place in the economies of the mountainous regions of Asia. At lower elevations, it is common to hybridize yaks with cattle to combine the yak’s hardiness with the productivity of cattle. Hybrid males are sterile, however, preventing the establishment of stable hybrid populations, but not a limited introgression after backcrossing several generations of female hybrids to male yaks. Here we inferred bovine haplotypes in the genomes of 76 Mongolian yaks using high-density SNP genotyping and whole-genome sequencing. These yaks inherited ~1.3% of their genome from bovine ancestors after nearly continuous admixture over at least the last 1,500 years. The introgressed regions are enriched in genes involved in nervous system development and function, and particularly in glutamate metabolism and neurotransmission. We also identified a novel mutation associated with a polled (hornless) phenotype originating from Mongolian Turano cattle. Our results suggest that introgressive hybridization contributed to the improvement of yak management and breeding

Genome-wide SNP typing of ancient DNA: Determination of hair and eye color of Bronze Age humans from their skeletal remains.

Objective A genome-wide high-throughput single nucleotide polymorphism (SNP) typing method was tested with respect of the applicability to ancient and degraded DNA. The results were compared to mini-sequencing data achieved through single base extension (SBE) typing. The SNPs chosen for the study allow to determine the hair colors and eye colors of humans. Material and methods The DNA samples were extracted from the skeletal remains of 59 human individuals dating back to the Late Bronze Age. The 3,000 years old bones had been discovered in the Lichtenstein Cave in Lower Saxony, Germany. The simultaneous typing of 24 SNPs for each of the ancient DNA samples was carried out using the 192.24 Dynamic Array (TM) by Fluidigm (R). Results Thirty-eight of the ancient samples (=64%) revealed full and reproducible SNP genotypes allowing hair and eye color phenotyping. In 10 samples (=17%) at least half of the SNPs were unambiguously determined, in 11 samples (=19%) the SNP typing failed. For 23 of the 59 individuals, a comparison of the SNP typing results with genotypes from an earlier performed SBE typing approach was possible. The comparison confirmed the full concordance of the results for 90% of the SNP typings. In the remaining 10% allelic dropouts were identified. Discussion The high genotyping success rate could be achieved by introducing modifications to the preamplification protocol mainly by increasing the DNA input and the amplification cycle number. The occurrence of allelic dropouts indicates that a further increase of DNA input to the preamplification step is desirable

Direct-to-consumer genetic testing

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