Chromosomal Abnormalities

Question 1

Reciprocal translocations

Answer 1

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)

Question 2

Triploidy

Answer 2

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

Question 3

Meiosis I Nondisjunction

Answer 3

Failure of chromosomes to separate properly during Meiosis I; the gamete with 24 chromosomes contains both the paternal and the maternal homologues

Question 4

Meiosis II Nondisjunction

Answer 4

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

Question 5

Mosaicism

Answer 5

Two or more different chromosome complements are present within an individual; most often numerical, resulting from nondisjunction in an early postzygotic mitotic division

Question 6

Robertsonian Translocation

Answer 6

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

Question 7

Most common cause of trisomies

Answer 7

Maternal nondisjunction during Meiosis I

Question 8

Maternal Age Effect (Two Hit Model)

Answer 8

Diminished recombination caused by a lack of chiasmata or mislocated chiasmata, followed by faulty segregation

Question 9

Maternal Age Effect (Cohesin Model)

Answer 9

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

Question 10

Paracentric Inversions

Answer 10

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

Question 11

Pericentric Inversions

Answer 11

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

Question 12

Robertsonian translocations most commonly involve which chromosome?

Answer 12

Chromosome 14; karyotypic notation “der” denotes a Robertsonian translocation

Question 13

Interstitial deletion (paracentric)

Answer 13

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

Question 14

Interstitial deletion (pericentric)

Answer 14

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

Question 15

Isochromosome

Answer 15

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

Question 16

Uniparental disomy

Answer 16

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

Question 17

Non-allelic homologous recombination (NAHR)

Answer 17

Recombination between blocks of segmental duplication on homologs during meiosis; may lead to microdeletion and microduplciation of unique region bracketed by duplications

Question 18

DUF1220 Domain

Answer 18

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

Question 19

Gametes of a reciprocal translocation carrier - Adjacent-1 pathway

Answer 19

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

Question 20

Gametes of a reciprocal translocation carrier - Adjacent-2 pathway

Answer 20

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