Chromo Abberations

Cards (17)

  • Meiosis
    1. Chromosome number is halved
    2. Recombination takes place
  • Failure during meiosis may result in a zygote with a chromosome imbalance after fertilisation
  • Non-disjunction

    Whole chromosomes fail to segregate, resulting in trisomy or monosomy (aneuploidy)
  • Accidents at meiosis can also result in chromosome rearrangements, duplications and deletions
  • Numerical aberrations

    • 47,+21 - Down syndrome
    • 47,+18
    • 47,+X - Turner syndrome
    • 47,+XXY - Klinefelter syndrome
    • 47, XXY
    • 47, XXX
  • Trisomy 21
    Extra chromosome = Down syndrome
  • Trisomy 18
    Extra chromosome = Edwards syndrome
  • Trisomy 18

    • Second most common autosomal trisomy in humans
    • Clinical symptoms: encompass prenatal growth deficiency, specific craniofacial features and other minor anomalies, major malformations, and marked psychomotor and cognitive developmental delay
    • Major causes of death: include central apnea, cardiac failure due to cardiac malformations, respiratory insufficiency due to hypoventilation, aspiration, or upper airway obstruction (and combinations)
  • Trisomy 13
    • Third common autosomal trisomy in humans
    • Very poor prognosis
    • >80% patients have severe cardiac defects
    • >50% of all patients have (also) CNS manifestations, including holosprosencephaly, deafness, microcephaly with sloping forehead, retinal dysplasia, abnormal auricle helices
    • Further malformations include the kidneys and the liver
    • Clinical symptoms: encompass prenatal growth deficiency, specific craniofacial features and other minor anomalies, major malformations, and marked psychomotor and cognitive developmental delays
  • Sex chromosomal abnormalities

    • Turner syndrome = 45, X - from father (monosomy)
    • Trisomy X - 47, XXX from mother
    • Klienfelter - 47, XXY from mother or father - trisomy
    • XYY - 47, XYY - from father - trisomy
  • Chromosome aberrations

    • Highlight the importance of gene dosage (no of copies of a given gene in a genome)
    • Aneuploidy can result in haploinsufficiency (monosomy) and triploabnormality (trisomy)
    • Effects of monosomy tend to be more severe than effects of trisomy → in part due to manifestations of recessive mutations
  • Chromosome mutations can result in a zygote with a chromosome imbalance after fertilisation
  • Non-disjunction is when whole chromosomes fail to segregate, resulting in either trisomy or monosomy (aneuploidy)
  • Structural chromosome aberrations

    • translocations - chromosome breaks and the (two) fragmented pieces re-attach to diff chromosomes
    • deletions - loss of genetic material (nucleotides)
    • inversions - a segment breaks, reattaches within the same chromos but in reverse oreintation
    • insertions - addition of nucleotides into chromos
    • duplications - one or more copies produced of a segment
    • isochromosomes - supernumerary marker chromosom made of 2 copies of the same arm of a chromos = leads to a tetrasomy
    • ring chromosomes - circular structure when a chromos breaks in 2 places and broken ends fuse together
  • Mechanisms for chromosome rearrangements

    1. Chromosome = double-stranded DNA molecule
    2. Any rearrangement is therefore preceded by double-stranded DNA break
    3. Repair systems may struggle with double-stranded DNA breaks
    4. For stability: chromosomes need to have one centromere and two telomeres
    5. Rearrangements are result of chromosome breakage and re-joining and can cause gene imbalance
  • Reciprocal translocation

    • 46, XX, t (11:22) (q23;q11,2)
    • Can be detected by pseudo-linkage
    • Loci from diff chromosomes = linked to each other on fusion chromosome
    • Balanced translocations = acentric fragments do not affect centromeres & usually non-pathogenic
  • Robertsonian translocation

    • 45,XY,t(14;21)(q10;q10)
    • Involves 2 acrocentric chromosomes (13, 14, 15, 21, 22)
    • New chromosome = stable and new translocation = non pathogenic
    • Total chromo number = reduced as causes problems in gametogensis and aneuploidies in offspring carrier