A comprehensive genetic map of the human genome based on 5,264 microsatellites

The cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene on 2q33 is associated with autoimmune thyroid diseases (AITDs). Our earlier study in 56 families showed linkage of 2q33 to the presence of thyroid antibodies (TAbs). The goals of this study were to confirm the linkage of the 2q33 region to TAbs, to fine map this region, and study the ICOS gene. We performed a linkage study in an expanded data set of 99 multiplex AITD-TAb families (529 individuals). The highest two-point LOD score of 2.9 was obtained for marker D2S325 on 2q33. To fine map this locus, we genotyped 238 Caucasian AITD patients and 137 controls for five additional markers in the linked locus, which contained the CTLA-4, CD28, and ICOS genes. The A/G singlenucleotide polymorphism at position 49 of CTLA-4 was associated with AITD (P¼0.01, OR¼1.5), while markers inside CD28 and ICOS were not. Functional studies have shown that the G allele was associated with reduced inhibition of T-cell proliferation by CTLA-4. We concluded that: (1) the AITD gene in the 2q33 locus is the CTLA-4 gene and not the CD28 or ICOS genes; and (2) the G allele is associated with decreased function of CTLA-4.

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“…This order and distances in cM were obtained from the Genethon maps, 34 and were confirmed in our data set.…”

Section: Resultssupporting

confidence: 83%

Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease

et al. 2003

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“…Positions of the markers, their levels of heterozygosity and distances were obtained from the Human Genome Database version March 15, 1996 (Dib et al, 1996). The allelic patterns of the markers were resolved on polyacrylamide gels after their ampli®cation using the polymerase chain reaction as previously described and compared between tumors and normal DNA samples of the same patient (Chaturverdi et al, 1997).…”

Section: Microsatillite Analysis Of 9p21mentioning

confidence: 99%

Level of retinoblastoma protein expression correlates with p16 (MTS-1/INK4A/CDKN2) status in bladder cancer

et al. 1999

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Recent studies have shown that patients whose bladder cancer exhibit overexpression of RB protein as measured by immunohistochemical analysis do equally poorly as those with loss of RB function. We hypothesized that loss of p16 protein function could be related to RB overexpression, since p16 can induce transcriptional downregulation of RB and its loss may lead to aberrant RB regulation. Conversely, loss of RB function has been associated with high p16 protein expression in several other tumor types. In the present study RB negative bladder tumors also exhibited strong nuclear p16 staining while each tumor with strong, homogeneous RB nuclear staining were p16 negative, supporting our hypothesis. To expand on these immunohistochemical studies additional cases were selected in which the status of the p16 encoding gene had been determined at the molecular level. Absent p16 and high RB protein expression was found in the tumors having loss of heterozygosity within 9p21 and a structural change (mutation or deletion) of the remaining p16 encoding gene allele, con®rming the staining results. These results strongly support the hypothesis that the RB nuclear overexpression recently associated with poor prognosis in bladder cancer is also associated with loss of p16 function and implies that loss of p16 function could be equally deleterious as RB loss in bladder and likely other cancers.

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“…Oligonucleotide primers described in Kwiatkowski and Diaz (1992), Weissenbach et al (1992), Wilkie et al (1992) and Gyapay Consensus intermarker distances in cM, sex-averaged, taken from Kwiatkowski et al (1993) and Dib et al (1996). Markers originally identified by AFM code have been given their current D9S code (brackets)…”

Section: Oligonucleotide Primersmentioning

confidence: 99%

Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive carcinoma of the breast

Marsh

Varley²

1998

Br J Cancer

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Summary Twenty-three cases of ductal carcinoma in situ (DCIS), ten of which had an associated invasive component, were studied for loss of heterozygosity (LOH) of microsatellite markers on chromosome 9p and the results compared with a panel of 20 invasive breast carcinomas. In addition to the gene encoding p16, chromosome 9p is also thought to contain other putative tumour-suppressor genes. If the three panels of breast tumours showed LOH of markers in this region this would suggest that such putative genes were important in breast carcinogenesis. By studying both preinvasive and invasive breast tumours, it should also be possible to gain further information about the relationship between lesions of a different stage and to determine whether DCIS is indeed a precursor of invasive ductal carcinoma. Levels of LOH were low in the invasive-only set of tumours. Surprisingly, considerably higher levels of loss were observed in the tumours with an in situ component. Also, much heterogeneity was observed between different DCIS ducts or invasive tumour and DCIS from the same case.

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A comprehensive genetic map of the human genome based on 5,264 microsatellites

Cited by 2,721 publications

References 13 publications

Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease

Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease

Level of retinoblastoma protein expression correlates with p16 (MTS-1/INK4A/CDKN2) status in bladder cancer

Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive carcinoma of the breast

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