Heritable Fragile Site on Chromosome 16: Probable Localization of Haptoglobin Locus in Man

Magenis, R. Ellen; Hecht, Frederick; Lovrien, Everett W.

doi:10.1126/science.170.3953.85

Cited by 120 publications

(46 citation statements)

References 7 publications

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“…2-12 copies of the distal portion of the long arm were found in some lymphocyte metaphase spreads (Magenis et al, 1970). Such chromosomal breakage leading to non-staining gaps of both chromatids and, in a subset of metaphases, to deleted chromosomes 16, acentric fragments and multiradial figures was thereafter observed in conventional cultures of spontaneous FRA16B by several other investigators (referenced in Schmid et al, 1986).…”

Section: Review Of the Morphologymentioning

confidence: 72%

“…FRA16B was originally described as a fully penetrant chromosomal marker which helped to localize the gene for the ·-polypeptide chain of haptoglobin on chromosome 16 (Magenis et al, 1970). Thereafter, this fragile site was observed in a variable proportion of lymphocyte metaphases from further cases (referenced in Schmid et al, 1980) and classified as non-folatesensitive (Sutherland, 1979a).…”

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confidence: 99%

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The rare human fragile site 16B

Felbor¹,

Feichtinger²,

Schmid³

2003

Cytogenet Genome Res

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The rare human fragile site 16B (FRA16B) has been found to occur spontaneously. Its expression in lymphocyte cultures can also be induced or greatly enhanced by addition of chemicals which are known to bind to AT-rich DNA regions. Following optimal treatment with 150 µg/ml berenil 24 h prior to fixation, the heterozygote frequency of FRA16B is found to be about 5% in populations of European descent. Thus, FRA16B represents the most common of the rare fragile sites. Consistent with cytogenetic observations, the molecular characterization of FRA16B revealed that it is an amplified 33-base pair AT-rich minisatellite repeat. These interindividually variable, extremely large repeat expansions of 15–70 kb in size do not seem to interfere with the expression of genes essential for human development since heterozygotes and homozygotes for FRA16B are normal.

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Section: Review Of the Morphologymentioning

confidence: 72%

mentioning

confidence: 99%

The rare human fragile site 16B

Felbor¹,

Feichtinger²,

Schmid³

2003

Cytogenet Genome Res

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“…The alpha-haptoglobin locus has been assigned to chromosome 16 (29), and one report places it on the long arm (30). It would be interesting to find families variant for both alpha haptoglobin and APRT and thereby test their linkage.…”

Section: Discussionmentioning

confidence: 99%

Assignment of the Gene for Adenine Phosphoribosyltransferase to Human Chromosome 16 by Mouse-Human Somatic Cell Hybridization

Tischfield

Ruddle

1974

Proc. Natl. Acad. Sci. U.S.A.

111

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A series of mouse-human hybrids was prepared from mouse cells deficient in adenine phosphoribosyltransferase (EC 2.4.2.7) and normal human cells. The hybrids were made in medium containing adenine and alanosine, an antimetabolite known to inhibit de novo adenylic acid biosynthesis. The mouse cells, unable to utilize exogenous adenine, were killed in this medium, but the hybrids proliferated as a consequence of their retaining the human aprt gene. The hybrids were then exposed to the adenine analogs 2,6-diaminopurine and 2-fluoroadenine to select for cells that had lost this gene. Before exposure to the adenine analogs, the expression of human adenine phosphoribosyltransferase by the hybrids was strongly associated only with the presence of human chromosome 16, and afterwards this was the only human chromosome consistently lost. This observation suggests that the human aprt gene can be assigned to chromosome 16.Mouse-human somatic cell hybrids are useful for genetic analysis because they progressively lose human chromosomes and the species origin of the chromosomes and a variety of cellular phenotypes can be distinguished. It is possible, therefore, to assign the genes for certain phenotypes to particular human chromosomes by noting the concordant presence or absence of a particular phenotype(s) and chromosome in many independent hybrid clones. Observations of the loss of the phenotype coincident to the loss of the human chromosome strengthen such assignments. Selective methods have been developed to enrich for hybrids in a mixed population of parental cells. Most notable is the HAT selective system of Littlefield (1), which allows hybrid survival by retention of a gene from each of the parental inputs. This subject has been reviewed by Ruddle (2).Studies have indicated that the locus for adenine phosphoribosyltransferase (APRT) is autosomally inherited (3), and electrophoretic variants have been reported (4). Kusano, Long, and Green (5) described a selection method where survival of mouse-human hybrids depended upon their retention of the human aprt gene. Mouse cells resistant to the adenine analogs 2,6-diaminopurine (DAP) and 2-fluoroadenine (FA), and consequently lacking APRT activity (APRT-), were hybridized to normal human cells in medium containing adenine and alanosine. Alanosine is an inhibitor Qualitative Assay for APRT. Mouse and human AIPRT were distinguished with an acrylamide gel electrophoresisautoradiographic method which is described elsewhere (10).Production and Analysis of Hybrids. The standard medium was Dulbecco-Vogt modified Eagle's medium supplemented with 10% heat-inactivated fetal-calf serum, 100 units/ml of penicillin, 100 gg/ml of streptomycin, and 100 4g/mnl of kanamycin, and equilibrated with 10% C02-90% air.Alanosine [L(-) 2-amino-3-nitrosohydroxylamino propi-45

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“…(3) The incidence is increased in chromosomal abnormalities such as partial deletion of the long or the short arm of chromosome 18 (Masterson and Law, 1969;Fischer et al, 1970;Jansch, May, and LaMarche, 1970;Stewart et al, 1970), ring formation 18 (Feingold et al, 1968;Peterson and Good, 1968;Murken, Salzer, and , trisomy 18 (Hecht, 1969), and heritable fragile site on chromosome 16 (Magenis, Hecht, and Lovrien, 1970 higher in patients with ataxia telangiectasia than in normal individuals (Eidelman and Davis, 1968;Peterson and Good, 1968 In several respects the IgA deficiency shows similarities to the aetiology of cleft lip and palate for which originally autosomal dominant, autosomal recessive and sex-linked modes of inheritance were postulated but where now a polygenic predisposition to the defect has been accepted as the most likely genetic mechanism to explain the occurrence of a familial tendency (Fraser, 1970). In chromosomal abnormalities the incidence of cleft lip and palate is also increased.…”

Section: Resultsmentioning

confidence: 99%

Genetic aspects of selective immunoglobulin A deficiency.

Grundbacher¹

1972

Journal of Medical Genetics

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Heritable Fragile Site on Chromosome 16: Probable Localization of Haptoglobin Locus in Man

Cited by 120 publications

References 7 publications

The rare human fragile site 16B

The rare human fragile site 16B

Assignment of the Gene for Adenine Phosphoribosyltransferase to Human Chromosome 16 by Mouse-Human Somatic Cell Hybridization

Genetic aspects of selective immunoglobulin A deficiency.

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