Mutation (genetic algorithm)

About: Mutation (genetic algorithm) is a research topic. Over the lifetime, 31223 publications have been published within this topic receiving 720553 citations.

Familial primary ovarian insufficiency associated with an SYCE1 point mutation: defective meiosis elucidated in humanized mice.

Abstract: More than 50% of cases of primary ovarian insufficiency (POI) and nonobstructive azoospermia in humans are classified as idiopathic infertility. Meiotic defects may relate to at least some of these cases. Mutations in genes coding for synaptonemal complex (SC) components have been identified in humans, and hypothesized to be causative for the observed infertile phenotype. Mutation SYCE1 c.721C>T (former c.613C>T)-a familial mutation reported in two sisters with primary amenorrhea-was the first such mutation found in an SC central element component-coding gene. Most fundamental mammalian oogenesis events occur during the embryonic phase, and eventual defects are identified many years later, thus leaving few possibilities to study the condition's etiology and pathogenesis. Aiming to validate an approach to circumvent this difficulty, we have used the CRISPR/Cas9 technology to generate a mouse model with an SYCE1 c.721C>T equivalent genome alteration. We hereby present the characterization of the homozygous mutant mice phenotype, compared to their wild type and heterozygous littermates. Our results strongly support a causative role of this mutation for the POI phenotype in human patients, and the mechanisms involved would relate to defects in homologous chromosome synapsis. No SYCE1 protein was detected in homozygous mutants and Syce1 transcript level was highly diminished, suggesting transcript degradation as the basis of the infertility mechanism. This is the first report on the generation of a humanized mouse model line for the study of an infertility-related human mutation in an SC component-coding gene, thus representing a proof of principle.

Joint nonparametric coalescent inference of mutation spectrum history and demography

Abstract: Booming and busting populations modulate the accumulation of genetic diversity, encoding histories of living populations in present-day variation. Many methods exist to decode these histories, and all must make strong model assumptions. It is typical to assume that mutations accumulate uniformly across the genome at a constant rate that does not vary between closely related populations. However, recent work shows that mutational processes in human and great ape populations vary across genomic regions and evolve over time. This perturbs the mutation spectrum: the relative mutation rates in different local nucleotide contexts. Here, we develop theoretical tools in the framework of Kingman’s coalescent to accommodate mutation spectrum dynamics. We describe mushi: a method to perform fast, nonparametric joint inference of demographic and mutation spectrum histories from allele frequency data. We use mushi to reconstruct trajectories of effective population size and mutation spectrum divergence between human populations, identify mutation signatures and their dynamics in different human populations, and produce more accurate time calibration for a previously-reported mutational pulse in the ancestors of Europeans. We show that mutation spectrum histories can be productively incorporated in a well-studied theoretical setting, and rigorously inferred from genomic variation data like other features of evolutionary history.

Mutable genes in the light of Callan's hypothesis of serially repeated gene copies.

Abstract: MUTABLE genes have been intensively studied in maize by McLintock1–3 and Brink4–6 and they occur widely in higher plants7. Among many features of mutable genes, all difficult to explain by conventional mutation theory, the following are especially relevant to the present discussion, (a) One original labile gene often gives rise with high frequency to a whole range of more or less stable alleles, quantitatively graded in their expression. (b) In addition, a labile gene can frequently mutate to other unstable alleles, differing from the original in the timing or frequency of mutation or in the kinds of stable derivatives most often produced, (c) The frequency of mutation is frequently drastically affected by changes of temperature (in several examples higher temperature causes reduced mutation frequency), or by genes elsewhere in the genotype; such variables affect the mutable gene specifically in the sense that they have no evident effect on mutation in general. All these features are well shown in the pallida-recurrens mutable system of Antirrhinum majus8,9. In the following discussion I shall refer to the Antirrhinum mutants because I am familiar with them, although McLintock has documented most of the same effects much more thoroughly in maize.