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Related Concept Videos

Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).Mechanisms of Genetic VariationThe original sources of genetic variation are mutations,...
Genome Size and the Evolution of New Genes03:21

Genome Size and the Evolution of New Genes

While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
Genome Size and the Evolution of New Genes03:21

Genome Size and the Evolution of New Genes

While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
Evolution of New Traits in Microbes01:24

Evolution of New Traits in Microbes

Microorganisms evolve rapidly due to their large population sizes and short generation times, often exhibiting measurable changes within days under laboratory conditions. Natural selection acts on standing genetic variation, enabling the retention and amplification of beneficial traits that confer fitness advantages in changing environments.Adaptive Pigment Regulation in RhodobacterIn Rhodobacter, a genus of purple non-sulfur bacteria, light-harvesting pigments such as bacteriochlorophyll and...
Genetics of Speciation02:16

Genetics of Speciation

Speciation is the evolutionary process resulting in the formation of new, distinct species—groups of reproductively isolated populations.The genetics of speciation involves the different traits or isolating mechanisms preventing gene exchange, leading to reproductive isolation. Reproductive isolation can be due to reproductive barriers that have effects either before or after the formation of a zygote. Pre-zygotic mechanisms prevent fertilization from occurring, and post-zygotic mechanisms...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...

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A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
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Selection and mutation in the "new" genetics: an emerging hypothesis.

Bruce Gottlieb1, Lenore K Beitel, Carlos Alvarado

  • 1Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote Ste. Catherine Road, Montreal, QC H3T 1E2, Canada. bruce.gottlieb@mcgill.ca

Human Genetics
|January 26, 2010
PubMed
Summary

Next-generation sequencing reveals genetic heterogeneity within tissues, uncovering multiple gene variants. This somatic mosaicism in normal and cancerous tissues may drive multifactorial diseases through selection, not just mutation.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Pathogenesis

Background:

  • Next-generation sequencing (NGS) offers enhanced sensitivity for studying multifactorial diseases.
  • Previous NGS applications focused on inter-individual genomic differences.
  • Intra-individual genetic variation within tissues remained largely unexplored.

Purpose of the Study:

  • To investigate genetic variation within individual human tissues using deep sequencing.
  • To identify and characterize somatic mosaicism at the gene variant level.
  • To propose a new hypothesis for multifactorial disease ontogeny.

Main Methods:

  • Utilized next-generation sequencing (NGS) for deep sequencing of tissues.
  • Employed massively parallel sequencing to achieve over 10,000x coverage.
  • Analyzed genetic variation within individual tissue samples.

Main Results:

  • Discovered intra-tissue genetic heterogeneity, characterized by majority and minority gene variants.
  • Identified this specialized somatic mosaicism in both normal and cancerous tissues.
  • Revealed widespread genetic variation within individual tissues.

Conclusions:

  • Somatic mosaicism, including majority and minority gene variants, is a significant factor in multifactorial disease development.
  • Selection of pre-existing somatic gene variants, rather than mutation alone, may be critical in disease ontogeny.
  • Changes in tissue microenvironments could drive the selection of these variants, impacting disease progression.