Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data.

Next-generation sequencing (NGS) technologies have become the standard for data generation in studies of population genomics, as the 1000 Genomes Project (1000G). However, these techniques are known to be problematic when applied to highly polymorphic genomic regions, such as the human leukocyte antigen (HLA) genes. Because accurate genotype calls and allele frequency estimations are crucial to population genomics analyses, it is important to assess the reliability of NGS data. Here, we evaluate the reliability of genotype calls and allele frequency estimates of the single-nucleotide polymorphisms (SNPs) reported by 1000G (phase I) at five HLA genes (HLA-A, -B, -C, -DRB1, and -DQB1). We take advantage of the availability of HLA Sanger sequencing of 930 of the 1092 1000G samples and use this as a gold standard to benchmark the 1000G data. We document that 18.6% of SNP genotype calls in HLA genes are incorrect and that allele frequencies are estimated with an error greater than ±0.1 at approximately 25% of the SNPs in HLA genes. We found a bias toward overestimation of reference allele frequency for the 1000G data, indicating mapping bias is an important cause of error in frequency estimation in this dataset. We provide a list of sites that have poor allele frequency estimates and discuss the outcomes of including those sites in different kinds of analyses. Because the HLA region is the most polymorphic in the human genome, our results provide insights into the challenges of using of NGS data at other genomic regions of high diversity

Development Of Polymorphic Microsatellite Markers For The Human Botfly, Dermatobia Hominis (diptera: Oestridae)

In this report, we describe the development of 17 polymorphic microsatellite markers for the human botfly, Dermatobia hominis, an obligatory parasite of mammals of great veterinary importance in Latin America. The number of alleles ranged from 5 to 21 per locus, with a mean of 12.2 alleles per locus. The expected heterozygosity ranged from 0.2571 to 0.9206 and from 0.2984 to 0.9291 in two populations from Brazil. These markers should provide a high resolution tool for assessment of the fine-scale genetic structure of natural populations of the human botfly. © 2009 The Authors.91409411Brookfield, J.F.Y., A simple new method for estimating null allele frequency from heterozygote deficiency (1996) Molecular Ecology, 5, pp. 453-455Edwards, K.J., Barker, J.H.A., Daly, A., Jones, C., Karp, A., Microsatellite libraries enriched for several microsatellite sequences in plants (1996) BioTechniques, 20, pp. 758-759Guimarães, J.H., Papavero, N.A., A tentative annotated bibliography of Dermatobia hominis (Linnaeus Jr., 1781) (Diptera: Cuterebridae) (1966) Arquivos de Zoologia, 14, pp. 223-294Raymond, M., Rousset, F., GenePop (version 1.2): Population genetics software for exact tests and ecumenicism (1995) Journal of Heredity, 86, pp. 248-249Rice, W.R., Analyzing tables of statistical tests (1989) Evolution, 43, pp. 223-225Rozen, S., Skaletsky, H.J., (1998) Primer3, , http://www-genome.wi.mit.edu/genome_software/other/primer3.html, Code available AtSancho, E., Dermatobia, the Neotropical warble fly (1998) Parasitology Today, 4, pp. 242-246Torres, T.T., Azeredo-Espin, A.M.L., Development of new polymorphic microsatellite markers for the New World screw-worm, Cochliomyia hominivorax (Diptera: Calliphoridae) (2005) Molecular Ecology Notes, 5, pp. 815-818Van Oosterhout, C., Hutchinson, W.F., Wills, D.P., Shipley, P., Micro-Checker: Software for identifying and correcting genotyping errors in microsatellite data (2004) Molecular Ecology Notes, 4, pp. 535-53

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus.

Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success