Abstract
The COL6A1 and COL6A2 (collagen VI) gene cluster on chromosome 21 is a candidate region for defects leading to congenital heart anomalies in Down's syndrome. We report a variable number of tandem repeats (VNTR) and a restriction fragment length polymorphism (RFLP) in this gene region, detected using a COL6A1 cDNA probe. Linkage disequilibrium relationships were studied among the RFLPs of this gene cluster. The RFLP reported here shows no significant linkage disequilibrium with any others in the region. It has a polymorphism information content value of 0.27, raising the informativity of the locus.
Similar content being viewed by others
References
Amento EP, Ehsani N, Palmer H, Libby P (1991) Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterio Thromb 11:1223–1230
Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map using restriction fragment length polymorphisms. Am J Hum Genet 32:314–331
Byers PH (1990) Brittle bones fragile molecules: disorders of collagen gene structure and expression. Trends Genet 6:293–300
Chu ML, Mann K, Deutzmann R, Pribula-Conway D, Hsu-Chen C-C, Bernard MP, Timpl R (1987) Characterization of three constituent chains of collagen type VI by peptide sequences and cDNA clones. Eur J Biochem 168:309–317
Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, Puffenberger EG, Hamosh A, Nanthakumar EJ, Curristin SM, Stetten G, Meyers DA, Francomano CA (1991) Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352:337–339
Duff K, Williamson R, Richards SJ (1990) Expression of genes encoding 2 chains of the collagen type-VI molecule during human fetal heart development. Int J Cardiol 27:128–129
Francomano CA, Cutting GR, McCormick MK, Chu ML, Timpl R, Hong HK, Antonarakis SE (1991) The COL6A1 and COL6A2 genes exist as a gene cluster and detect highly informative DNA polymorphisms in the telomeric region of human chromosome 21q. Hum Genet 87:162–166
Haviland MB, Kessling AM, Davignon J, Sing CF (1991) Estimation of Hardy-Weinberg and pairwise disequilibrium in the apolipoprotein AI-CIII-AIVC gene cluster. Am J Hum Genet 40:350–365
Jander R, Rauterberg J, Glanville RW (1983) Further characterization of the three polypeptide chains of bovine and human short-chain collagen. Eur J Biochem 133:39–46
Kessling A, Ouellette S, Bouffard O, Chamberland A, Betard C, Selinger E, Xhignesse M, Lussier-Cacan S, Davignon J (1982) Patterns of association between genetic variability in apolipoprotein (apo) B, apo AI-CIII-AIV, and cholesterol ester transfer protein gene regions and quantitative variation in lipid and lipoprotein traits: influence of gender and exogenous hormones. Am J Hum Genet 50:92–106
Kunkel LM, Smith DK, Boyer SH, Borgaonkar SD, Wachtel SS, Miller OJ, Breg WR, Jones HW Jr, Rary JM (1977) Analysis of Y chromosome specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 74:1245–1249
Kurnit DM, Layton WM, Matthysse S (1987) Genetics, chance and morphogenesis. Am J Hum Genet 41:979–995
Murata Y, Yoshioka H, Kitaoka M, Iyama K, Okamura K, Usuku G (1990) Type-VI collagen in healing rabbit corneal wounds. Ophthalmic Res 22:144–151
Rand JH, Patel ND, Schwartz E, Zhou SL, Potter BJ (1991) 150-kD Von Willebrand factor binding protein extracted from human vascular subendothelium is type-VI collagen. J Clin Invest 88:253–259
Smith DW (1976) Recognizable patterns of human malformation, 2nd edn. Saunders, Philadelphia, p 7
Timple R, Engel J (1987) Typ VI collagen. In: Mayne R, Burgeson RE (eds) Structure and function of collagen types. Academic Press, New York, pp 105–143
Tromp G, Kuivanierni H, Shikata H, Prockop DJ (1989) A single base mutation that substitutes serine for glycine 790 of the al (III) chain of type III procollagen exposes an arginine and causes Ehlers-Danlos syndrome IV. J Biol Chem 264:1349–1352
Weil D, Mattei M-G, Passage E, Cong NV, Pribula-Conway D, Mann K, Deutzmann R, Timpl R, Chu ML (1988) Cloning and chromosomal localisation of human genes encoding the three chains of type VI collagen. Am J Hum Genet 42:435–445
Weir BS, Cockerham CC (1989) Complete characterization of disequilibrium at two loci. In: Feldman MW (eds) Mathematical evolutionary theory. Princeton University Press, Princeton. pp 86–110
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Davies, G.E., Howard, C.M., Gorman, L.M. et al. Polymorphisms and linkage disequilibrium in the COL6A1 and COL6A2 gene cluster: novel DNA polymorphisms in the region of a candidate gene for congenital heart defects in Down's syndrome. Hum Genet 90, 521–525 (1993). https://doi.org/10.1007/BF00217452
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00217452