Assessing Genetic Risks: Implications for Health and Social Policy

Abstract

Book reviews plification and sequencing are shown in the figure .A first strand cDNA synthesis kit (Pharmacia) with poly-T primer and specific COX8 primer (F 1-22) was used for cDNA amplification between nucleotides 22 and 472 (figure A), according to the nucleotide numbers reported by Rizzuto et al.7 The 5' end of COX8 cDNA, before nucleotide 22, was amplified with the 5'-RACE kit (Life Tech- nology/Gibco-BRL) and specific COX8 primer (R 231-250, figure B).Overlapping PCR fragments were sequenced using the dideoxynucleotide chain termination method with fluorescent dideoxynucleotides on an Applied Biosystem 373A DNA sequencer (Perkin Elmer/ABI).We found a hitherto unidentified sequence of 42 nucleotides at the 5' end of the cDNA, and the rest of the COX8 cDNA sequence was identical to that previously described by Rizzuto et al7 (figure).From nucleotides -42 to + 472, there were no mutations in either the affected or healthy people in the COX8 cDNA.The promoter region of the COX8 gene, the part of the gene that has not yet been identified, was not analysed.However, all the mutations so far identified in FHC have been described, either in the coding regions of the gene (mutations in MYH7 encoding the 13 myosin heavy chain3), or in an intronic splicing site (mutation in the splice donor se- quence of intron 15 of the cardiac troponin T gene5).By analogy with all the data avail- able for FHC, we therefore conclude that the COX8 gene is very unlikely to be the disease gene of the CMH4 locus responsible for FHC.We are indebted to the family members for their invaluable participation.