Chapter 82

Genetic factors play a significant role in all cardiovascular disorders (see also Chap. 10). Genetic defects are responsible for malformations of the heart and blood vessels, which account for the largest number of human birth defects. The estimated incidence of congenital heart disease is approximately 1% of all live births.1 The prevalence is estimated to be 10-fold higher among stillbirths.2 Genetic defects are responsible for familial cardiovascular disorders, such as cardiomyopathies and the long QT (LQT) syndrome, as well as nonfamilial sporadic forms. Evidence is now becoming available indicating genetic predisposition for common complex phenotypes, such as atherosclerosis and hypertension. Molecular genetics in conjunction with cytogenetics provide the opportunity to decipher the genetic basis and pathogenesis of cardiovascular diseases. Given the rapid pace of genetic discoveries, it is expected that genetic diagnosis and screening will become incorporated into standard practice in the near future. It is thus imperative that cardiologists understand the basis for genetic disorders and the medical and ethical implications of genetics.

### Basis for Genetic Transmission

All hereditary information is transmitted through DNA, a linear polymer composed of purine (adenine, guanine) and pyrimidine (cytosine, thymine) bases. The gene is the basic hereditary unit. It consists of a distinct fragment of DNA, which encodes a specific polypeptide (protein). There are approximately 30,000 genes in the human genome.3 Each individual has two copies of each gene, called alleles. The genes are localized in a linear sequence along 23 pairs of chromosomes, including 22 pairs of autosomes (chromosomes 1 to 22) and 1 pair of sex chromosomes, X and Y. Females have two X chromosomes, whereas males carry one X and one Y chromosome. Each parent contributes one of each chromosome pair (the members of the pair are referred to as homologous chromosomes) and thus one copy of each gene. The site at which a gene is located on a particular chromosome is referred to as the genetic locus. A given gene always resides at the same genetic locus on a particular chromosome, so the loci on homologous chromosomes are identical. However, alleles residing at these loci may be identical or different, leading to homozygous (identical alleles) and heterozygous (two different alleles present at the locus) states.

The genetic information is encoded by the linear sequence of the four bases of the DNA. Translation of this information into protein is through a translational code passed on through messenger ribonucleic acid (mRNA). Each unit of three bases, referred to as a codon, encodes a specific amino acid. The transcribed mRNA serves as the template that determines the sequence of the amino acids in the resulting polypeptide. Both autosomal alleles are usually transcribed into mRNA and translated into protein. However, expression of a gene can be restricted to specific cells and organs or regulated during a developmental stage because of regulation by cell- and tissue-specific transcription factors. In cells that carry two X ...

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