Multifactorially inherited conditions, accounting for 20% 4.
Disorders that show an unusual pattern of inheritance, accounting for 2% to 3% 5.
Conditions caused by exposure to teratogens, accounting for 6%
DNA is composed of four nucleotide building blocks: adenine, guanine, cytosine, and thymine. Each nucleotide islinked to other nucleotides, forming a chain. The DNA molecule consists of two chains of nucleotides held togetherby hydrogen bonds. The purine nucleotides, adenine andguanine, cross-link by hydrogen bonds to the pyrimidines,thymine and cytosine. Because of this cross-linking, thenucleotide sequence of one strand sets the other strand’s sequence. Separating the two strands permits complementary nucleotides to bind to each DNA strand; this copies theDNA and replicates the sequence.
DNA exists as multiple fragments that, together with a protein skeleton (chromatin), form chromosomes. Human cells have 23 pairs of chromosomes, with one copy of each chromosome inherited from each parent. Twenty-two pairs of chromosomes are autosomes; the remaining pair is called the sex chromosomes. Females have two X chromosomes; males have one X and one Y.
Spread along the chromosomes, like beads on a string,DNA sequences form genes, the basic units of heredity. Atypical gene contains a promoter sequence, an untranslatedregion, and an open reading frame, all arrayed from the 5′ to the 3′ end of the DNA. In the open reading frame, everythree nucleotides represent a single codon, coding for a particular amino acid. In this way, the sequence of bases dictatesthe sequence of amino acids in the corresponding protein.Some codons, rather than coding for a specific amino acid,act as a “start” signal, whereas others serve as “stop” signals. Between the start and stop codons, genes consist oftwo major portions: exons, regions containing the code thatultimately corresponds to a sequence of amino acids, andintrons (intervening sequence), which do not become partof the amino acid sequence.
Genes are transcribed into messenger RNA (mRNA), then translated into proteins. During transcription, RNA is processed to remove introns. The mRNA serves as a template to construct the protein.
Human genetic material contains 3.1 billion bases. Lessthan 2% of the DNA codes for proteins, comprising thegenome’s approximately 21,000 genes. Through a mechanism called alternative splicing, these 21,000 genes maycreate more than 100,000 proteins. The remainder of theDNA, the portion not involved in protein formation, hadbeen termed junk DNA, but a project called ENCODE(Encyclopedia of DNA Elements) found that much of thispresumed junk DNA is functional and likely serves some regulatory function.
Disease may be caused by changes or mutations in the DNA sequence, with the point mutation, a change in a single DNA base, being the most common type. A point mutation that changes a codon and the resulting amino acid thatgoes into the protein is referred to as a missense mutation. A nonsense mutation is a point mutation that changes thecodon to a “stop” codon so that transcription stops prematurely. A frameshift mutation often stems from the loss or addition of one or more DNA bases; this causes a shift in how the DNA is transcribed and generally leads to premature stop codons.
To identify specific patterns of inheritance, geneticists construct and analyze pedigrees, which are pictorial representations of a family history. Males are represented by squares and females by circles. Matings are connected with a solid line between each partner’s symbols. Unmarried couples are often connected by a dashed line. Children from a couple are represented below their parents and are the next generation.