Chromosomal Abnormalities Flashcards
Reciprocal translocations
An exchange of segments between non-homologous chromosomes; meiosis procedes through formation of a quadrivalent figure by one of three mechanisms: alternatate (normal/balanced translocation gametes), adjacent 1, and adjacent 2 (partial trisomy/monomy gametes)
Triploidy
Cells are 3n; may result either from fertilization by 2 sperm (dispermy) or failure of one of the meiotic divisions, resulting in a diploid egg or sperm; infants may be liveborn but do not live long
Meiosis I Nondisjunction
Failure of chromosomes to separate properly during Meiosis I; the gamete with 24 chromosomes contains both the paternal and the maternal homologues
Meiosis II Nondisjunction
Failure of chromosomes to separate properly during Meiosis II; the gamete with the extra chromosome contains both copies of either the paternal or maternal sister chromatids
Mosaicism
Two or more different chromosome complements are present within an individual; most often numerical, resulting from nondisjunction in an early postzygotic mitotic division
Robertsonian Translocation
Fusion of two acrocentric chromosomes near the centromere region with loss of the short arms containing multiple copies of genes for rRNA (usually not deleterious and thus considered ‘balanced’); may segregate via a trivalent structure along 3 pathways to produce normal/balanced gametes or partially trisomic/monomic gametes
Most common cause of trisomies
Maternal nondisjunction during Meiosis I
Maternal Age Effect (Two Hit Model)
Diminished recombination caused by a lack of chiasmata or mislocated chiasmata, followed by faulty segregation
Maternal Age Effect (Cohesin Model)
Degradation of cohesin complexes throughout the course of extended Meiosis I arrest in oocytes, allowing “terminalization” of chiasmata toward the ends of homologs and premature separation of the homologs and/or sister chromatids
Paracentric Inversions
Inversions of a region of a chromosome excluding the centromere; crossover may generate both dicentric and acentric chromosomes in gametes
A class of balanced rearrangement
Pericentric Inversions
Inversions of a region of a chromosome including the centromere; crossover may result in chromosomes with duplications and deletions in gametes
A class of balanced rearrangement
Robertsonian translocations most commonly involve which chromosome?
Chromosome 14; karyotypic notation “der” denotes a Robertsonian translocation
Interstitial deletion (paracentric)
A class of unbalanced chromosomal rearrangement; produces one chromosome with lost genetic material in the region of the deletion, and one acentric fragment (linear or ring) that is not stably transmissible
Interstitial deletion (pericentric)
Deletion of a region of a chromosome spanning the centromere; results in two acentric fragments (not stably transmissible) and a stably transmissible centric ring (marker) chromosome
Isochromosome
A chromosome in which one arm is missing and the other arm is duplicated in a mirror-like fashion; may result from exchange between one arm of a chromosome and its homologue or by misdivision through the centromere in Meiosis II
Uniparental disomy
Abnormal phenotypes associated with genetic imprinting errors; most often occurs as a result of trisomy followed by loss of the extra chromosome leaving either 2 maternal or 2 paternal chromosomes, where normal development is dependent on expression of genes at the missing loci
Non-allelic homologous recombination (NAHR)
Recombination between blocks of segmental duplication on homologs during meiosis; may lead to microdeletion and microduplciation of unique region bracketed by duplications
DUF1220 Domain
A repetitive region of DNA found on 1q21; increased copy numbers are associated with larger brain size, and instability of this region is maintained
Duplications –> Macrocephaly & autism
Deletions –> Microcephaly & Schizophrenia
Gametes of a reciprocal translocation carrier - Adjacent-1 pathway
Adjacent-1 pathway leads to the formation of two unbalanced gametes with segregated homologs; following fertilization, each gamete will be partially trisomic & partially monosomic for one of the chromosomes involved in the translocation
Gametes of a reciprocal translocation carrier - Adjacent-2 pathway
Adjacent-2 leads to the formation of two unbalanced gametes in which homologs are unsegregated (one gamete receives both copies of one chromosome, the other gamete receives both copies of the other chromosome); following fertilization, each gamete will be partially trisomic & partially monosomic for one of the chromosomes involved in the translocation
