Numerical and Structural Chromosomal Abnormalities Flashcards
Describe mitosis (as compared to meiosis)
One round of chromosome segregation; daughter cells identical in chromosomal content to the parental cell. DNA replication precedes each round of chromosome segregation. No pairing of homologous chromosomes. Infrequent recombination. Centromeres on paired sister chromatids segregate at each anaphase. Occurs in somatic cells and in germ line precursor cells prior to entry into meiosis
Describe meiosis (as compared to mitosis)
Two rounds of chromosome segregation without an intervening round of DNA replication. Parental cells must be diploid and the chromosome number is halved in the resultant cells. Requires the pairing of homologous chromosomes and recombination. Centromeres on paired sister chromatids divide only at anaphase II. Occurs only in the germ line
Name 3 categories of human chromosomes (based on cetromere)
Metacentric (centromere in middle; two arms are equal length). Submetacentric (centromere not quite in middle). Acrocentric (centromere near one end)
Euploidy
“Good ploidy:” full set of chromosomes - 46
Polyploidy
“Many ploidy:” Triploid - 69. Tetraploid - 92
Aneuploidy
“Not good ploidy.” Trisomy - 47. Monosomy - 45
Autosomal monosomies vs. monosomatic at X chromosome
Autosomal monosomies do not survive. BUT 45 X can survive (Turner syndrome)
Where do most errors occur that lead to trisomies?
Generally; maternal errors in 1st meiotic division
What are the effects on gametes if nondisjunction occurs in meiosis I?
All gametes are abnormal. Either 2n or 0n.
What are the effects on gametes if nondisjunction occurs in meiosis II?
Half of gametes are abnormal. 2 gametes will be normal (n); 1 will be 2n; 1 will be 0n
Describe relationship between crossing-over and nondisjunction
Crossover events that occur too near or too far from the centromere increase chromosome nondisjunction. Centromere-distal appears to lead to errors in meiosis I; proximal appears to lead to errors in MII. Nondisjunction events are also related to the frequency of crossover events (reduction of recombination events increases likelihood of nondisjunction).
What kind of aneuploidies are tolerated at birth?
Trisomy 13; 18; 21. Sex chromosome aneuploidy
Describe Down syndrome
47; XY (or XX); +21. Trisomy 21. Characteristic facies; short stature; hypotonia; moderate intellectual disabilities; cardiac anomalies; leukemia in infancy.
Describe Edwards syndrome.
47; XY (or XX); +18. Trisomy 18. Small for gestational age; small head; clenched fingers; rocker-bottom feet.
Describe Patau syndrome
47; XY (or XX); +13. Trisomy 13. Characteristic facies; severe intellectual disabilities. Congenital malformations � holoprosencephaly; facial clefts; polydactyly; renal anomalies
Describe Turner syndrome
45; X. Short stature; webbed neck; edema of hands and feet; broad shield-like chest; narrow hips; renal and cardiovascular anomalies; gonadal dysgenesis (failure of ovarian maintenance). Many (25%) Pts have mosaicism (thought to contribute to survival).
Describe Klinefelter syndrome
47; XXY. Tall stature; hypogonadism; elevated frequency of gynecomastia; high frequency of
sterility; language impairment
Describe mosaicism
2 or more different cell karyotypes from the same individual. Most commonly caused by nondisjuction in early embryonic development.
Germ-line mosaicism
Result of mitotic nondisjunction in germ cell precursor
Balanced vs. unbalanced structural rearrangements
Balanced: intrachromosomal rearrangements; no loss or gain of genetic information; usually normal phenotype. Unbalanced: loss or gain of genetic info; usually abnormal phenotype.
What are the 3 main types of balanced rearrangements?
Inversions (pericentric and paracentric); reciprocal translocation; Robertsonian translocation
General description of 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. Pericentric and paracentric
What is a pericentric inversion?
It includes the centromere
Describe what can occur with a pericentric inversion during meiosis
A loop is formed. If crossing over occurs at the edges there is not an issue (both chromosomes are balanced). Baby will be healthy; 50% will be carriers of the inversion. If the crossover occurs within the loop chromosomes produced will be unbalanced; both will lose some genes and have duplicates of other genes. Baby will either be lost or if carried to term will have defects.
