Month: May 2016

Tutorial

The genetic sex-determination system predicts adult sex ratios in tetrapods

Genetic sex determination, i. e. the determination of sexual phenotypes by the effect of sex-determining genes, is found in the majority of vertebrates. Sex determination genes have evolved multiple times independently and can be located on different chromosomes. Depending on whether the presence of the sex determining region (SDR) determines female or male sex, genetic systems of sex determination are called ZW or XY systems respectively and the sex which is heterozygous for the SDR is called the heterogametic sex. Lower fitness in the heterogametic sex has long been observed in interspecific hybrids in a wide range of animal and even plant species, an observation called Haldane’s rule. In this paper the authors find a similar pattern in (non-hybrid) tetrapod species: by comparing the adult sex ratio in XY and ZW systems in 344 tetrapod species, they find that the ASR is skewed towards the homogametic sex (towards females in an XY system and towards males in a ZW system). This observation is based on a dataset containing known genetic sex determination systems and adult sex ratios (ASRs) of species across the vertebrate phylogeny. Within amphibians and reptiles (in which both XY and ZW systems are found), the authors show …

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Genomics / Human

Identification of a large set of rare complete human knockouts

High throughput genotyping and sequencing has led to the discovery of numerous sequence variants associated to human traits and diseases. An important type of variants involved are Loss of Function (LoF) mutations (frameshift indels, stop-gain and essential sites variants), which are predicted to completely disrupt the function of protein-coding genes. In case of Mendelian recessive diseases, for the condition to occur, the LoF variants must be biallelic, i.e. affecting both copies of a gene. The affected gene is then defined as “knockout”. By studying the Icelandic population, authors aim to identify rare LoF mutations (Minor Allele Frequency, MAF < 2%) present in individuals participating in various disease projects. They then investigate at which frequency in the population these LoF mutations are homozygous (i.e. knockout) in the germline genome. The Icelandic population Iceland is well-suited for genetic studies for three main reasons. The island was colonized by human population around the 9th century by 8-20 thousand settlers. Since then the population grew to around 320’000 inhabitants today. The initial founder effect and rare genetic admixture make the Icelandic population a genetic isolate. In addition to an unusual genetic isolation, Iceland’s population benefits of a genealogical database containing family histories reaching centuries …

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Evolution / Genomics / Tutorial

Supergenes and social organization in a bird species

      Cindy Dupuis, Xinji Li, Casper van der Kooi   The development of new molecular mechanisms and next generation sequencing techniques have advanced our knowledge on the genetic basis underlying phenotypic polymorphism. Over the coarse of recent years, scientific studies have documented large genomic regions with drastic phenotypic effects, the so-called supergenes. A supergene is a set of genes on the same chromosome that exhibit close genetic linkage and thus inherits as one unit. The evolution of a supergene requires that multiple loci with complementary effects become linked (i.e. they are genetically clustered and recombination between the loci is suppressed) and that optimal alleles at the linked loci are combined. Genetic clustering of different loci can occur when, via mutation, an adaptive interaction between two closely placed loci is created. In addition, gene duplications or translocations that generate a series of (novel) complementary genes can give rise to supergenes. The probability of a recombination event occurring in between loci depends on various factors. The chance of a recombination event occurring in between two loci will be small when the loci are located closely together, as the chance of a recombination event in between two loci generally decreases with …

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