Diagnosis of Human Genetic Diseases

Restriction enzymes, such as Hpa I were used in a study on sickle-cell anemia. The probe hybridized in normal hemoglobin with two fragments 7000 or 7600 nucleotides long. Sickle-cell hemoglobin had hybridization with a 13,000 nucleotide single sequence. A similar result has been obtained from amniocentesis studies, providing a tool to screen fetus and adult for sickle-cell. The markers where hybridization occurred are referred to as RFLPs (restriction-fragment-length polymorphisms). The longer fragment in sickle-cell individuals is interpreted as evidence of a mutation in the recognition sequence. Two nucleotide sequences close together on the same DNA molecule tend to stay together. In the sickle-cell DNA the beta-chain hemoglobin gene has become linked with another gene that somehow alters the recognition sequence at which Hpa I hybridizes. Heterozygotes will have both long and short fragments, while a single type (short or long) will occur in homozygous dominant and recessive, respectively.
Huntington's disease was studied by James F. Gusella and his research team, who used RFLPs to identify a marker. Testing a large library of human DNA fragments, Gusella et al. found the needle in the haystack. The enzyme used was Hind III. Four fragments have been identified in an American family that has members suffering from the disease. The presence of fragment A has been identified in individuals who suffer from (or will suffer from) Huntington's. Pattern A occurs in 60 percent of the population, as well as the Huntington's sufferers. A Venezuelan family of 3000 members is descended from a German sailor who had Huntington's. This family had a strong correlation between Fragment C and the disease. Pattern C is much less common among the general population in this country. Many individuals do not wish to know if they will develop this disease; Woody Guthrie's children have chosen not to be tested.
Cystic fibrosis (CF) has also been studied with RFLP technology. CF is the most common genetic disease in Caucasia