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PMID: 1371263 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Intra- and extragenic marker haplotypes of CFTR mutations in cystic fibrosis families.

Human genetics ·Vol. 88 ·No. 4 ·1992-02-00 ·Pages 417-25

Dörk T, Neumann T, Wulbrand U, Wulf B, Kälin N, Maass G, Krawczak M, Guillermit H, Ferec C, Horn G

Abstract

In order to facilitate the screening for the less common mutations in the cystic fibrosis (CF) gene viz., the CF transmembrane conductance regulator gene (CFTR), marker haplotypes were determined for German non-CF (N) and CF chromosomes by polymerase chain reaction analysis of four polymorphisms upstream of the CF gene (XV-2c, KM.19, MP6-D9, J44) and six intragenic polymorphisms (GATT, TUB9, M470V, T854T, TUB18, TUB20) that span the CFTR gene from exon 6 through exon 21. Novel informative sequence variants of CFTR were detected in front of exons 10 (1525-61 A or G), 19 (3601-65 C or A), and 21 (4006-200 A or G). The CF locus exhibits strong long-range marker-marker linkage disequilibrium with breakpoints of recombination between XV-2c and KM.19, and between exons 10 and 19 of CFTR. Marker alleles of GATT-TUB9 and TUB18-TUB20 were found to be in absolute linkage disequilibrium. Four major haplotypes encompass more than 90% of German N and CF chromosomes. Fifteen CFTR mutations detected on 421 out of 500 CF chromosomes were each identified on one of these four predominant 7-marker haplotypes. Whereas all analysed delta F508 chromosomes carried the same KM.19-D9-J44-GATT-TUB9-M470V-T854T haplotype, another frequent mutation in Germany, R553X, was identified on two different major haplotypes. Hence, a priori haplotyping cannot exclude a particular CF mutation, but in combination with population genetic data, enables mutations to be ranked by decreasing probability.

Related Genes
CFTR
MeSH Terms
Alleles Base Sequence Cystic Fibrosis/blood,genetics Cystic Fibrosis Transmembrane Conductance Regulator DNA/blood,genetics,isolation & purification Exons Genetic Linkage Genetic Markers Germany Haplotypes Humans Introns Membrane Proteins/genetics Molecular Sequence Data Mutation Oligodeoxyribonucleotides Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Repetitive Sequences, Nucleic Acid
Chemicals
CFTR protein, human Genetic Markers Membrane Proteins Oligodeoxyribonucleotides Cystic Fibrosis Transmembrane Conductance Regulator DNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Dörk T
Abteilung Biophysikalische Chemie, Medizinische Hochschule, Hannover, Federal Republic of Germany.
Neumann T
Wulbrand U
Wulf B
Kälin N
Maass G
Krawczak M
Guillermit H
Ferec C
Horn G
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Article Info
Journal
Human genetics
Abbr.
Hum Genet
ISSN
0340-6717
DOI
10.1007/BF00215676
Published
1992-02-00
Pages
417-25
Language
English
Region
Germany
NLM ID
7613873
Subset
IM
Databases
GENBANK
S78409, S78411, S78413, S78753, S83234, S83236, S83238, S83241, S83242, S83243
External Links
PubMed source DOI: 10.1007/BF00215676 View journal details
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