Summary
Restriction fragment length polymorphic probes are being used more frequently in the molecular analysis of Down's syndrome and in the origin of nondisjunction in the syndrome. The type of information gained from RFLPs overlaps but differs from the information from cytogenetic heteromorphisms. From the allele frequencies of commonly available probes we have derived the expected frequencies of all matings in the population. Each mating has been defined and partitioned to show the genotypes and phenotypes expected, with numerical values based on studies with heteromorphisms. From this we show how the various phenotypes can be used to calculate the origin of nondisjunctions and their expected frequencies. Further, an alternative method is outlined for mapping the distance between a probe and its centromere based on the distortion, caused by crossing-over, of the expected 1st to 2nd division nondisjunction ratio. Finally, we discuss prospects for various uses of probes in the analysis of Down's syndrome.
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References
Antonarakis SE, Chakravarti A, Warren AC, Slaugenhaupt SA, Wong C, Halloran SL, Metaxotou C (1986) Reduced recombination rate in chromosomes 21 that have undergone nondisjunction. Cold Spring Harbor Symp Quant Biol 51:185–190
Bond DJ, Chandley AC (1983) Aneuploidy. (Oxford monographs on medical genetics) Oxford University Press, Oxford
Charlesworth B, Langley CH, Stephan W (1986) The evolution of restricted recombination and the accumulation of repeated DNA sequences. Genetics 112:947–962
Côté GB, Edwards JH (1975) Centromeric linkage in autosomal trisomies. Ann Hum Genet 39:51–59
Davis KE, Harper K, Bonthron D, Krumlauf R, Polkey A, Pembry ME, Williamson R (1984) Use of a chromosome 21 cloned DNA probe for the analysis of non-disjunction in Down syndrome. Hum Genet 66:54–56
Delabar JM, Huzet JL, Aurias A, Nicole A, Berthier M, Tanzer J, Sinet PM (1986) Down's syndrome with triplication of a region of chromosome 21 containing the CuZn superoxide dismutase gene without detectable caryotype abnormality. 7th International Congress of Human Genetics, Berlin 1986, part I, p 91
Ellis WG, McCulloch JR, Canley CL (1974) Presenile dementia in Down's syndrome: ultrastructural identity with Alzheimer's disease. Neurology 24:101–106
Gusella JF (1986) DNA polymorphisms and human disease. Annu Rev Biochem 55:831–854
Hassold TJ, Jacobs PA (1984) Trisomy in man. Annu Rev Genet 18:69–97
Hassold TJ, Chiu D, Yamane JA (1984) Parental origin of autosomal trisomies. Ann Hum Genet 48:129–144
Henderson SA, Edwards RG (1968) Chiasma frequency and maternal age in mammals. Nature 218:22–28
Hofker MH, Skraastad MI, Bergen AAB, Wapenaar MC, Bakker E, Millington-Ward AM, Van Ommen GJB, Pearson PL (1986) The X chromosome shows less genetic variation of restriction sites than the autosomes. Am J Hum Genet 39:438–451
Jacobs PA (1977) Human chromosome heteromorphisms (variants). Prog Med Genet 2:251–274
Jacobs PA, Morton NE (1977) Origin of human trisomies and polyploids. Hum Hered 27:59–72
Kittur SD, Antonarakis SE, Tanzi RE, Meyers DA, Chakravarti A, Groner Y, Phillips JA, Watkins PC, Gusella JF, Kazazian HH (1985) Initial construction of a linkage map of chromosome 21. (8th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 8:187 (abstr no 187)
Langenbeck U, Hansmann I, Hinney B, Hönig V (1976) On the origin of the supernumerary chromosome in autosomal trisomies with special reference to Down's syndrome. Hum Genet 33:89–102
Laurie DA, Hultén MA (1985) Further studies on bivalent chiasma frequency in human males with normal caryotypes. Ann Hum Genet 49:189–201
Licznerski G, Lindsten J (1972) Trisomy 21 in man due to maternal nondisjunction during the first meiotic division. Hereditas 70: 153–154
Manning CH, Goodman HO (1981) Parental origin of chromosomes in Down's syndrome. Hum Genet 59:101–103
Marklund SL (1986) Superoxide dismutase in human tissues, cells and extracellular fluids: clinical implications. In: Johnson JE, Walford R, Hartman D, Miguel J (eds) Free radicals, aging and degenerative diseases, vol 8. Liss, New York, pp 509–526
Martin G (1978) Genetic syndromes in man with potential relevance to the pathology of ageing. In: Bergsma D, Harrison DE (eds) Genetic effects on aging. Liss, New York
Mikkelsen M (1982) Down syndrome: current stage of cytogenetic epidemiology. In: Bonné-Tamir B, Cohen T, Goodman RM (eds) Human genetics, part B: Medical aspects. Proceedings of the 6th International Congress of Human Genetics. (Progress in clinical and biological research, vol 103B) Liss, New York, pp 297–307
Mikkelsen M, Poulson H, Grinsted J, Lange A (1980) Non-disjunction in trisomy 21: study of chromosomal heteromorphisms in 110 families. Ann Hum Genet 44:17–28
Niebuhr E (1974) Down's syndrome: the possibility of a pathogenetic segment on chromosome 21. Humangenetik 21:99–101
Olson MI, Shaw CW (1969) Pre-senile dementia and Alzheimer's disease in Down's syndrome. Brain 92:147–156
Oster J, Mikkelsen M, Nielsen A (1975) Mortality and life-table in Down's syndrome. Acta Paediatr Scand 64:322
Patterson D (1987) Genetic mapping in chromosome 21 and its implications for Down's syndrome and other diseases. Somatic Cell Genet 13:365–371
Robinson JA (1973) Origin of extra chromosome in trisoym 21. Lancet I:131–133
Rowe RD, Ushida JA (1961) Cardiac malformations in mongolism: a prospective study of 184 mongloid children. Am J Med 31:726–733
Rowley JD (1981) Down's syndrome and acute leukemia; increased risk may be due to trisomy 21. Lancet II:1020–1022
Scholl T, Stein Z, Hansen H (1982) Leukemia and other cancers, anomalies and infections as causes of death in Down's syndrome in the US during 1976. Dev Med Child Neurol 24:817–829
Southern EM (1982) Application of DNA analysis to mapping the human genome. Cytogenet Cell Genet 32:52–57
St George-Hyslop PH, Tanzi RE, Palinsky RJ, Haines JL, Nee L, Watkins PC, Myers RH, Feldman RG, Pollen D, et al (1987) The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science 235:885–890
Stewart GD, Berg AB, Lee F, Watkins PC, Paika I, Hassold T, Kurnit DM (1986) Molecular fine structure of the centromere region of chromosome 21. Am J Hum Genet 39:A222 (abstr)
Tandon R, Edwards J (1973) Cardiac malformation associated with Down's syndrome. Circulation 47:1349–1358
Tanzi R, Watkins P, Gibbons K, Faryniarz A, Wallace M, Hallewell R, Conneally PM, Gusella J (1985) A genetic linkage map of human chromosome 21. (8th International Workshop on Human Gene Mapping). Cytogenet Cell Genet 40:760
Ugazio AG, Maccario R, Duse M, Burgio GR (1977) T lymphocyte deficiency in Down's syndrome. Lancet I:1062
Wahrmann J, Goitein R, Richler C, Goldman B, Akstein E, Chaki R (1974) The mongoloid phenotype in man is due to trisomy of the distal pale G-band of chromosome 21. In: Pearson PL, Lewis KR (eds) Chromosomes today, vol 5. Wiley, New York, pp 241–248
Warren AC, Chakravarti A, Wong C, Slaugenhaupt SA, Halloran SL, Watkins PC, Metaxotou C, Antonarakis SE (1987) Evidence for reduced recombination on the nondisjoined chromosomes 21 in Down syndrome. Science 237:652–654
Watson DK, McWilliams-Smith MJ, Kozak C, Reeves R, Gearhart J, Nunn MF, Nash W, Fowle III JR, Duesberg P, Papas TS, O'Brien SJ (1986) Conserved chromosomal positions of dual domains of the ets protooncogene in cats, mice, and humans. Proc Natl Acad Sci USA 83:1792–1796
Willard HF, Skolnick M, Pearson PL, Mandel JL (1985) Human gene mapping by recombinant DNA techniques. (8th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 40: 360–489
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Millington-Ward, A.M., Pearson, P.L. Use of restriction fragment length polymorphic probes in the analysis of Down's syndrome trisomy. Hum Genet 80, 362–370 (1988). https://doi.org/10.1007/BF00273652
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DOI: https://doi.org/10.1007/BF00273652