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Flashcards in The changing genome Deck (26)

Clonal evolution and dynamic patterns observed


What is the estimated loss of Y in the ULSAM cohort?



What are other terms for Post-Zygotic variants?

  • somatic mosaicism
  • somatic variation
  • post-zygotic aberrations
  • detectable clonal mosaicism


How many repeats have minisatellites?

6-100bp up to 30kb 

  • Also referred to as VNTR


Name sources of genetic variation

  • base substitutions: SNPs, SNVs
  • indels
  • Copy number variants: SV (structural variation)
  • UPD -  uniparental disomy: CNNLOH (copy number neutral loss of heterozygosity)
  • VNTR: microsatellites, minisatellites
  • inversions
  • translocation
  • segmental duplication
  • chromosomal rearrangements
  • aneuploidies


Which de novo variants have the biggest mutational load?

Structure variants (SV)

deletions, insertions, translocations, ...


Name techniques that can asses genetic variation in the medium range

  • array based approaches
    • CGH- and SNP arrays
  • Copy number variation


Name techniques that can evaluate genetic variation in big ranges

  • Karyotyping
  • FISH
  • rearrangements
  • aneuploidies


What is loss of chromosome Y (LOY) associated with?

  • shorter survival
  • higher risk of cancer


What kind of aberrations accumulate with age?

  • large-scale aberrations (>1 Mbp)
  • small-scale variants


What is fetal microchimerism?

  • bidirectional exchange of fetal and maternal cells during pregnancy:
    • mum gets cells from the kid into her
    • kid gets ectra cells from the mum into it
    • siblings could get cells from child 1 as well
    • cell traffic increases in quantity throughout gestational period


What are germline variants (GV)?

Mutations/Variants that follow mendelian laws of inheritance.

  • It is inherited from germline to zygote and all cells derived from the zygote in the F1 generation.
  • Needs to arise in a germline cell in order to be passed on.
  • most frequently studies type of mutation in GWAS and genome projects (95%)


What is revertant mosaicism (RM)?

A process where a variant disappears; a back-mutation.


What is a De Novo Variant (DNV) of the germline?

Arises in a germline cell of the parent and is present somatically in the F1 generation

  • only F1 has it, not parent
  • becomes germline variant when inherited to F2
  • well studied in trios and pedigrees


What are post zygotic variants (PZV)?

Variants that are acquired during life time in somatic cell

  • occur after first cell division, all cells arising from that cell carry it
  • it is intragenerational: rises in a specific lineage within a soma and disappears when orgininal carrier cell/provider dies
  • not really studied, even though driver in disease processes
  • they can change in frequency over time


What is an indel?

Up to 20bp are missing or added


What is somatic mosaicism?

A mix of cell lineages with different genotypes within the soma of a single subject.

Applicable for both de novo and post-zygotic variants


What is copy number nutral loss of heterozygosity?

It is also called UDP: uniparental disomy

Parts of one chromosome are lost completely, but the other chromosome is used as template to rescue that region. For the region rescued, there is only one allele present, but twice.
There is no loss of fragments, therefore copy number neutral


What makes up the total load of mutations TLM?

  • germline variants: following mendelian laws of inheritance
  • de novo variants of the germline
  • post zygotic variants: acquired during life time
  • microchimerism
  • revertant mosaicism


What are trinucleotide repeat expansions?

Dynamic mutations that suddenly change size; between parent and child but also within individuals


What is the predicted range of post-zygotic genetic variation in the adult human body?

more than 10^16
(point mutations; the others probably in the same range)

based on:

  • mutation rate of 10^-8
  • 6 billion bps in diploid genome
  • 100 trillion cells per soma


What about large scale autosomal aberrations during aging?

  • deltions: change
  • CCNLOH: change
  • gains: do not change


Which de novo variations are the most frequent?

Single nucleotide variants - SNV


How many repeats have microsatellites?

2-6bp repeat motives, repeated 5-50 times

  • high mutation rate
  • high diversity in the population
  • classified as VNTR (variable number of tandem repeats)


Name techniques that can evaluate genetic variation in a small range
(1kb to 1bp)

  • VNTRs
  • microsatellites
  • minisatellites


How many of the elderly are affected by post-zygotic structure variants?

more than 20%
not well studied in younger populations