Gene mapping and chromosome 21: history and methodology.
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Biomedical subjects
Publications and source records attributed to E B Robson.
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A family with two nucleoside phosphorylase-deficient patients has been scored for the segregation of NP0 and the variable region 14p. The mose likely 14p:NP recombination fraction is 0.15 in males and 0.30 in females. There is no family data to assign the Pi:Gm linkage group to chromosome 14, but as immunoglobulin heavy chain has been assigned to this chromosome by somatic cell methods the most likely gene order is 14p:NP:Pi:Gm with Pi in 14q2 and Gm in 14(q23 leads to q32), but the order 14p:NP:Gm:Pi with Pi in 14(q24 leads to qter) and Gm in 14(q22 leads to q24) is not excluded. The available linkage data between biochemical markers on acrocentric chromosomes and their short arm markers suggest that there may be more recombination towards the ends of human chromosomes whether or not those ends carry centromeres.
A 69,XXX liveborn baby was shown to have the Rh genotype CDe/cDE/cde which suggested that 46 of her chromosomes were of paternal origin. Studies on C band polymorphisms and other genetic markers indicated that the most likely origin of this triploid was a failure of male meiosis II.
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The segregation of human phosphoglycolate phosphatase has been studied in 52 independent human-rodent hybrids and 69 subclones. The results suggest that human PGP is on chromosome 16. Family data suggest that PGP is not close to 16qh or alpha Hp. The most likely regional assignment for PGP would appear to be 16p13 or 16p12, but a site on 16q cannot be entirely excluded. New data on 16qh and alpha Hp suggest that the male recombination fraction between these loci is about 0.2.
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The locus for hereditary angio-oedema must lie well outside the limits of the HLA complex. Linkage tests with 16 marker loci gave no hint of linkage. In particular, close linkage is excluded for C6, PGM1 MNSs, Gm, Rh, Km, Hp, and ABO.
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Some families with abnormalities of chromosome 9 have been combined with others from the literature to show that AK1 and ABO must lie near the end of that chromosome. Current evidence suggests that both lie in band 9q34. MNSs, GPT and Gc can be excluded from chromosome 9.
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A technique using computerized data handling for following the fate of 125I-fibrinogen through various physiological compartments is presented. Its use in detecting fibrin build up in patients with metastatic tumors and cancer-caused DIC is explained. An increase in j3u (fractional catabolic rate as seen in the urine data) throughout the course of a study was found to be an important indicator of extravascular fibrin build up.
We have failed to measure the recombination fraction between 9qh and the ABO:AK1 linkage group. Since the total male map distance along chromosome 9 is likely to be at least 120 cM, calculated from male chiasmata counts (Hultén, 1974) they may well not be within measurable distance of each other. ACONs does not lie between ABO and AK1, but there is so little information on this marker from family studies that it could lie almost anywhere else on chromosome 9 and might be within measurable distance of 9qh. The map of chromosome 9 based on studies on families with normal karyotypes is summarized in Fig. 1. We hope to improve this map in a subsequent paper based on observations on families with abnormal karyotypes.
Family studies show that alphaFUC is closely linked to Rh and confirm that the locus for alpha-L-fucosidase is on chromosome 1.
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