A genetic linkage map of human chromosome 21: analysis of recombination as a function of sex and age.
A genetic linkage map of human chromosome 21 has been constructed using 22 anonymous DNA markers and five complementary DNAs (cDNAs) encoding the amyloid beta protein precursor (APP), superoxide dismutase 1 (SOD1), the ets-2 proto-oncogene (ETS2), the estrogen inducible breast cancer locus (BCEI), and the leukocyte antigen, CD18 (CD18). Segregation of RFLPs detected by these DNA markers was traced in the Venezuelan Reference Pedigree (VRP). A comprehensive genetic linkage map consisting of the 27 DNA markers spans 102 cM on the long arm of chromosome 21. We have confirmed our initial findings of a dramatically increased rate of recombination at the telomere in both females and males and of significantly higher recombination in females in the pericentromeric region. By comparing patterns of recombination in specific regions of chromosome 21 with regard to both parental sex and age, we have now identified a statistically significant downward trend in the frequency of crossovers in the most telomeric portion of chromosome 21 with increasing maternal age. A less significant decrease in recombination with increasing maternal age was observed in the pericentromeric region of the chromosome. These results may help in ultimately understanding the physical relationship between recombination and nondisjunction in the occurrence of trisomy 21.
Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Charlestown 02129.
R E
RE
Tanzi
P C
PC
Watkins
G D
GD
Stewart
N S
NS
Wexler
J F
JF
Gusella
J L
JL
Haines
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002503:Centromere; D002874:Chromosome Mapping / Q000379:methods*; D002891:Chromosomes, Human, Pair 21; D003434:Crossing Over, Genetic / Q000235:genetics; D015342:DNA Probes; D005260:Female; D005786:Gene Expression Regulation; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D009630:Nondisjunction, Genetic; D010331:Paternal Age; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D000090063:Proto-Oncogene Mas; D011995:Recombination, Genetic / Q000502:physiology*; D012737:Sex Factors; D016615:Telomere
D015342:DNA Probes; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas