Structural Chromosomal Abnormalities Flashcards
Balanced rearrangement
Individuals with balanced rearrangements have normal complements of chromosomal material, meaning there is no loss of genetic material. However, these rearrangements have varying stabilities during meiosis and mitosis.
Inversion
occurs when one chromosome undergoes two double strand breaks of the DNA backbone and the intervening sequence is inverted prior to the rejoining of the broken ends
Paracentric inversions ________ the centromere
exclude
Pericentric inversions ________ the centromere
include
Reciprocal translocation
results from the breakage and rejoining of non-homologous chromosomes, with a reciprocal exchange of the broken segments
Alternate segregation produces
gametes that have either the normal chromosome complement or two reciprocal translocation chromosomes, both of which are balanced with respect to chromosome complement
Robertsonian translocation
the fusion of two acrocentric chromosomes within their centromeric regions, resulting in the loss of both short arms (containing rDNA repeats)
Unbalanced rearrangement
the chromosome set has additional or missing material. Phenotypes of these individuals are likely to be abnormal. Duplication of genetic material in gametes can lead to partial trisomy after fertilization with a normal gamete, while deletions lead to partial monosomy
Deletion
loss of genetic information that can arise by simple chromosome breakage and rejoining, unequal crossing over between misaligned homologous chromosomes or sister chromatids, or by abnormal segregation of a balanced translocation or inversion
Chromosomal rearrangements require ________ and can be induced by ________
two DNA double strand breaks (DSBs)
a variety of DNA damaging agents
disease associated with reciprocal translocation
chronic myelogenous leukemia
disease associated with a deletion
Cri-du-chat syndrome
duplication
gain of genetic information, which is generally less harmful than deletion, but can lead to abnormalities (i.e. partial trisomy 21).
Ring Chromosome
a chromosome fragment that circularizes and acquires kinetochore activity for stable transmission to daughter cells (also called a marker chromosome)
Isochromosome
a chromosome in which one arm is missing and the other duplicated in a mirror-image fashion, possibly occurring through an exchange involving one arm of a chromosome and its homolog at the proximal edge of the arm, adjacent to the centromere
A small percentage of Down syndrome patients have the 21q21q ________
isochromosome
Most chromosome structural abnormalities found in fetuses and newborns that are associated with serious clinical effects are attributable to ________
a random event
Occasionally a serious chromosomal abnormality can be inherited from a seemingly normal parent who carries a ________ such as a translocation. In these comparatively rare cases, the recurrence risk could be much ________
balanced chromosomal abnormality
increased
Contiguous gene syndromes
abnormal phenotypes caused by over-expression or loss (haploinsufficiency) of neighboring genes
Wolf-Hirschhorn syndrome
- deletion
- facial clefting, prominent ears, microcephaly, intellectual disabilities
Beckwith-Wiedemann syndrome
- duplication
- paternal
- overgrowth, omphalocele, predisposition to Wilms, other tumors
Cri du chat syndrome
- deletion
- microcephaly, characteristic cry, seizures, intellectual disabilities
Angelman syndrome
- deletion
- maternal
- seizures, intellectual disabilities
Williams syndrome
- deletion
- congenital heart disease, short stature
Prader-Willi syndrome
- deletion
- paternal
- hypotonia, hypopigmentation, hypogenitalism, obesity
Langer-Giedion syndrome
- deletion
- Tricho-rhino-pharangeal syndrome, multiple exostoses
Miller-Dieker syndrome
- deletion
- lissencephaly (agyria), profound intellectual disabilities
WAGR syndrome
- deletion
- Wilms tumor, aniridia, genitourinary anomalies, intellectual disabilities
DiGeorge syndrome
- deletion
- absent or hypoplastic thymus and parathyroids, congenital heart disease, Velo-Cardio-Facial syndrome, cleft palate, lateral nasal buildup, cardiac septal defects
