1-32 Introduction to Cytogenetics Flashcards
What is a syndrome?
- Set of characteristics which occur together and are assumed to have a common basis
- Not all characteristics occur in all affected individuals
- Range of variability within a population
What is the difference between numerical and structural chromosomal abnormalities?
Numerical abnormalities are a change in the total number of chromosomes of the set, e.g., a gain or loss of chromosomes (monosomy X, triploidy).
Structural abnormalities are a change in the size/shape of one or more chromosomes, e.g., deletion, translocation, etc.
What are the types of samples used most commonly in cytogenic studies, and why might each one be used?
- Blood: the easiest and least painful
- Bone marrow: usu. for oncology studies
- Tissue: can be obtained by skin biopsy in a living individual, but is most commonly used when a karyotype is needed for a deceased individual
- Amniotic fluid and chorionic villi: prenatal specimens
What is the basic morphology of a chromosome?
Each double helix is termed a chromatid; the two chromatids are held together by the centromere, which also acts as a landmark and divides the chromosome into arms (p arm = shorter arm, q arm = longer arm). When the centromere is approximately equidistant from both ends, the chromosome is said to be metacentric, but if it is closer to one end than the other, the chromosome is submetacentric.
An acrocentric chromosome has modified short arms with stalks containing only multiple copies of rRNA genes that are capped by a satellite (modified telomere). The end of a chromosome is the telomere, which is composed of the repeated DNA sequence (TTAGGG)n that functions to stabilize the chromosomes. There is a shortening of the telomeres over time, which has been postulated to lead to an increase in chromosomal aberrations that may, in part, be responsible for the human aging process.
What are the major landmarks used to identify chromosomal abnormalities in karyotype analysis?
- Size
- Centromere position
- Banding pattern
The banding pattern is the most specific, as each pair of chromosomes has a unique banding pattern.
What is a chromosomal polymorphism?
Normal chromosomal variation: the presence of 2+ alternative structural forms for a chromosome within a population. These are inherited as Mendelian characters and can be traced through pedigrees. The variation is usually not associated with specific clinical anomalies or a particular disease.
What is the process/ploidy of mitosis?
Mitosis is somatic division that proceeds as follows:
2N –> 4C –> 2N
What is the process of ploidy/DNA content in meiosis?
Meiosis is germ cell division that proceeds as follows:
2N –> 4C –> 2N –> N
What is nondisjunction?
Failure of the chromosomes or chromatids to disjoin properly. In meiosis, nondisjunction can occur at either the 1st or 2nd division, and the net result is different.
What is disomy?
The presence of 2 chromosomes, typically following nondisjunction during meiosis.
- Isodisomy: 2 chromosomes from the same source –> duplication of 1 chromosome
- Heterodisomy: 2 different chromosomes
ex) below: the first 2 cells are heterodisomic for A1/A2; second 2 cells are nullosomic for A1/A2.
What is euploidy?
Exact multiples of the haploid set of chromosomes.
NOTE: triploidy (3N) and tetraploidy (4N) are not compatible with life in humans.
What is aneuploidy?
Gain or loss of chromosomes equaling less than one complete complement. Usu. due to meiotic/mitotic nondisjunction error, not inheritance.
-
Trisomy: 2N + 1 = 47
Trisomy 13: 47,XX,+13 -
Monosomy: 2N - 1 = 45
Monosomy 8: 45,XY,-8 - Sex chromosomes:
45,XX
47,XXY
What are the viable autosomal trisomies?
- Trisomy 21: Down syndrome
- Trisomy 13: Patau syndrome
- Trisomy 18: Edwards syndrome
Despite its often severe clinical consequences, Down syndrome is usually quite manageable, and patients live into the second or third decade of life. Trisomy 13 and trisomy 18 are considerably less compatible with life; patients usually die within the first month of life. If an individual survives the first year, the outlook is bleak, since patients do not learn to talk, walk, or care for themselves.
What is Trisomy 21? What are its clinical features and possible system defects?
Trisomy of chromosome #21, which causes Down syndrome.
- Clinical features: short stature, low set ears, microcephaly, mental retardation, up slanting eyes, short hands, eye folds, protruding tongue, usu. infertile
- System defects: heart, lung, brain, endocrine system (infertility), susceptibility to infectious disease (15X), increased risk of leukemia (10X), high frequency of Alzheimer disease. More problems may arise as individual ages
What is Trisomy 13, and what are its clinical features?
Trisomy of chromosome #13, which causes Patau syndrome. Clinical features include:
- Failure to thrive
- Cleft lip and palate
- Rocker bottom feet
- Polydactyly
- “Punched-out” scalp
- Small head
- Heart defect
What determines sex?
A complex biochemical pathway involving the interaction of proteins produced by genes present on the autosomes and the X and Y chromosomes.
Females lack the TDF/SRY, so, ovaries will develop followed by differentiation of the Müllerian ducts. If the TDF/SRY is present and active, on the other hand, male development ensues. Testes develop, resulting in inhibition and degeneration of the Müllerian ducts.
