Genetic Susceptibility to Neonatal Disease

After completing this article, readers should be able to: 1. Define fundamental genetic terms. 2. Provide examples of DNA variation in the population. 3. Describe how DNA variation may contribute to disease susceptibility. 4. Describe the two designs of genetic epidemiology studies and the limitations of each. 5. Delineate the ethical considerations of genetic research. The sequencing of the human genome has revolutionized how we think about genetic variation between individuals. Comparison of DNA sequence across the human genome between individuals has revealed extensive variation in nucleotide sequence. Neonatology is rich with examples of infants who, despite similar risk factors, have different diseases, different disease severities, different responses to medication, and ultimately different outcomes. It now is believed that differences in DNA sequence may contribute to differences in individual characteristics, responses to drugs, or susceptibility to disease. As our understanding of genomic medicine grows, so may our ability to provide individualized medicine. Table 1 lists some common genetic terms used in this article. More than 3 gigabases of DNA encode the blueprint for approximately 35,000 genes. Genes are organized into regulatory regions called promoters, coding regions called exons, and intervening sequences between exons called introns. DNA is transcribed into RNA that then is translated into the amino acids that comprise proteins. Every cell contains two copies of each autosome and two sex chromosomes, one inherited from each parent. The DNA sequence of a gene may differ, and alternative forms of a gene are referred to as alleles. Homozygous individuals have the same alleles for a given gene. Heterozygous individuals have different alleles for a given gene. DNA variants in an individual represent a genotype; the clinical manifestations of DNA variants are the phenotype. | Allele | An alternative form or variant of a gene | || | Codon | A three-base sequence of DNA or RNA that specifies a single amino acid | | Exon | A region of a gene that codes for a protein | | Genomics | The study of the functions and interactions of all the genes in the genome, including their interactions with environmental factors | | Genotype | A person’s genetic identity, as reflected by his or her DNA sequence | | Haplotype | A group of nearby alleles that are inherited together | | Heterozygous | Possessing two different alleles at a specific gene locus | | Homozygous | Possessing two identical alleles at a specific gene locus | | Intron | A region of a gene that does not code for a protein | | Linkage disequilibrium | The nonrandom association of alleles at nearby loci in a population | | Monogenic | Caused by a mutation in a single gene | | Multifactorial | Caused by the interaction of multiple genetic and environmental factors | | Phenotype | The observable traits or characteristics of an organism associated with a specific gene, environmental factors, or both | | Single nucleotide polymorphism | A common nucleotide variant in the genome sequence | * Adapted from Guttmacher 2003 and the “talking glossary” of genetic terms available at: http://www.nhgri.nih.gov/glossary.cfm. Table 1. Glossary of Common Genetic Words DNA variation …