Chinese researchers have identified a new and simple method to identify women who may be carriers of the gene that causes hemophilia A. Being able to diagnose a female carrier means that better genetic counseling can be offered to families, helping them to make informed decisions about family planning.
The study, “Evaluation of factor VIII polymorphic short tandem repeat markers in linkage analysis for carrier diagnosis of hemophilia A,” was published in the journal Biomedical Reports.
Hemophilia A is caused by mutations in a gene called factor VIII that is situated on the X-chromosome. These mutations result in an essential blood-clotting protein to be defective or completely absent, causing increased bleeding.
Due to the complexity of the FVIII gene, it is difficult to recognize the disease-causing mutation with simple genetic tests.
Researchers led by Dr. F. Zheng from the Center for Gene Diagnosis at Zhongnan Hospital, Wuhan University, analyzed two generations of a Chinese family, where the son had hemophilia A, the father was healthy, the mother was a carrier, and the daughter was a suspected carrier of hemophilia A.
They used a technique called rapid multifluorescent polymerase chain reaction (PCR), and a seven short tandem repeat (STR) markers found inside and outside the factor VIII gene, to conduct a linkage analysis of the family, and determine whether or not the girl was a carrier.
Linkage analysis is an indirect method used to identify the probability of a faulty gene being passed to the next generation. Genes tend to be passed on together with other DNA sequences or markers that are found in close physical proximity to them. Therefore, analyzing the presence of such markers in a member of a family can help predict whether that family member has also inherited the faulty gene.
STRs are short repetitive sequences of about two to five DNA letters that are repeated many times in a head to tail manner. They are commonly used as genetic markers to do linkage analysis.
Results showed that for the seven STR markers, the haplotype (or group of genes) in the son and in the mother were identical. The sister carried the same haplotype as her brother, which came from the mother.
The researchers concluded that the STR markers used in this study were informative for linkage analysis, could differentiate pathogenic and healthy haplotypes among the family members, and identify the sister as a potential carrier of hemophilia A.