TY - JOUR
T1 - Fluorescent multiplex microsatellites used to define haplotypes associated with 75 CFTR mutations from the UK on 437 CF chromosomes
AU - Hughes, David
AU - Taylor, Joanne
AU - Wallace, Andrew
AU - Tassabehji, May
AU - McMahon, R
AU - Hill, Alison
AU - Nevin, Norman
AU - Graham, Colin
PY - 1996
Y1 - 1996
N2 - The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene contains three highly informative microsatellites: IVS8CA, IVS17bTA, and IVS17bCA. Their analysis improves prenatal/ carrier diagnosis and generates haplotypes from CF chromosomes that are strongly associated with specific mutations. Microsatellite haplotypes were defined for 75 CFTR mutations carried on 437 CF chromosomes (220 for delta F508, 217 for other mutations) from Northern Ireland and three English regions: the North-West, East Anglia, and the South. Fluorescently labelled microsatellites were amplified in a triplex PCR reaction and typed using an ABI 373A fluorescent fragment analyser. These mutations cover all the common and most of the rare CF defects found in the UK, and their corresponding haplotypes and geographic region are tabulated here. Ancient mutations, delta F508, G542X, N1303K, were associated with several related haplotypes due to slippage during replication, whereas other common mutations were associated with the one respective haplotype (e.g., G551D and R560T with 16-7-17, R117H with 16-30-13, 621 + 1G > T with 21-31-13, 3659delC with 16-35-13). This simple, fast, and automated method for fluorescent typing of these haplotypes will help to direct mutation screening for uncharacterised CF chromosomes.
AB - The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene contains three highly informative microsatellites: IVS8CA, IVS17bTA, and IVS17bCA. Their analysis improves prenatal/ carrier diagnosis and generates haplotypes from CF chromosomes that are strongly associated with specific mutations. Microsatellite haplotypes were defined for 75 CFTR mutations carried on 437 CF chromosomes (220 for delta F508, 217 for other mutations) from Northern Ireland and three English regions: the North-West, East Anglia, and the South. Fluorescently labelled microsatellites were amplified in a triplex PCR reaction and typed using an ABI 373A fluorescent fragment analyser. These mutations cover all the common and most of the rare CF defects found in the UK, and their corresponding haplotypes and geographic region are tabulated here. Ancient mutations, delta F508, G542X, N1303K, were associated with several related haplotypes due to slippage during replication, whereas other common mutations were associated with the one respective haplotype (e.g., G551D and R560T with 16-7-17, R117H with 16-30-13, 621 + 1G > T with 21-31-13, 3659delC with 16-35-13). This simple, fast, and automated method for fluorescent typing of these haplotypes will help to direct mutation screening for uncharacterised CF chromosomes.
KW - Chromosomes, Human
KW - Cystic Fibrosis
KW - Cystic Fibrosis Transmembrane Conductance Regulator
KW - Female
KW - Geography
KW - Great Britain
KW - Haplotypes
KW - Heterozygote Detection
KW - Humans
KW - Microsatellite Repeats
KW - Mutation
KW - Point Mutation
KW - Pregnancy
KW - Prenatal Diagnosis
UR - http://hdl.handle.net/2160/12652
U2 - 10.1002/(SICI)1098-1004(1996)8:3<229::AID-HUMU6>3.0.CO;2-4
DO - 10.1002/(SICI)1098-1004(1996)8:3<229::AID-HUMU6>3.0.CO;2-4
M3 - Article
C2 - 8889582
SN - 1059-7794
VL - 8
SP - 229
EP - 235
JO - Human Mutation
JF - Human Mutation
IS - 3
ER -