[The power of linkage analysis on PAH gene in prenatal gene diagnosis is improved with three additional short tandem repeat markers].
OBJECTIVE
To increase the success rate of prenatal diagnosis for classical phenylketonuria(PKU).


METHODS
Three new short tandem repeat (STR) markers (PAH26, PAH32 and PAH9) within and surrounding phenylalanine hydroxylase(PAH) gene were selected for amplified fragment length polymorphism. The allele frequencies and polymorphism information contests (PIC) were determined in Chinese population.


RESULTS
The PIC of these three new STR markers was 0.518 (PAH26), 0.413 (PAH32) and 0.362 (PAH9) respectively. There was linkage disequilibrium between PAH9 marker and PAH-STR marker (TCTA)n in the intron 3 of PAH gene. The linkage phase of the mutant genes and the markers was established using the combination of PAH-STR, PAH26 and PAH32 in 95% families. Prenatal diagnosis was performed successfully with these markers in four cases.


CONCLUSIONS
By selecting or combining the three STR markers, the mutant genes could be distinguished from the normal allele in up to 95% of families with classical PKU.
Department of Medical Genetics, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences and School of Basic Medicine, Beijing, 100005 P. R. China.
Feng-xia
FX
Yao
Hui
H
Guo
Juan-juan
JJ
Han
Yan
Y
Meng
Nian-hu
NH
Sun
Shang-zhi
SZ
Huang
D000483:Alleles; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
D010651:Phenylalanine Hydroxylase