Inheritance of some common traits: Freckles, dimples, widow's peak, hairy elbows, and a cleft chin.
The particular combination of genes in a person's genome constitutes the genotype (je'no-tlp). The appearance or health condition of the individual that develops as a result of the ways the genes are expressed is termed the phenotype (fe'no-tlp). An allele is wild-type if its associated phenotype is either normal function or the most common expression in a particular population. Wildtype is indicated with a + sign. An allele that is a change from wild-type, perhaps producing an uncommon phenotype, is mutant. Disease-causing alleles are mutant.
For many genes, in heterozygotes, one allele determines the phenotype. Such an allele whose action masks that of another allele is termed dominant. The allele whose expression is masked is recessive. Dominant alleles are usually indicated with a capital letter. A gene that causes a disease can be recessive or dominant. It may also be autosomal (carried on a nonsex chromosome) or X-linked (carried on the X chromosome) or Y-linked (carried on the Y chromosome). The more general and older term "sex-linked" refers to a gene on the X or Y chromosome.
Whether a trait is dominant or recessive, autosomal or sex-linked is called its mode of inheritance. This designation has important consequences in predicting the chance that offspring will inherit an illness or trait. The following rules emerge:
1. An autosomal condition is equally likely to affect either sex. X-linked characteristics affect males much more often than females, a point we will return to later in the chapter in the section titled "Sex Chromosomes and Their Genes."
2. A person most likely inherits a recessive condition from two parents who are each heterozygotes (carriers). The parents are usually healthy. For this reason, recessive conditions can "skip" generations.
3. A person who inherits a dominant condition has at least one affected parent. Therefore, dominant conditions do not skip generations. (An exception is if the dominant allele arises, as a new mutation, in the sperm or egg.) If, by chance, a dominant trait does not appear in a generation in a particular family, it does not reappear in subsequent generations, as a recessive trait might.
Cystic fibrosis is an example of an autosomal recessive disorder. The wild-type allele for the CFTR gene, which is dominant over the disease-causing allele, specifies formation of protein chloride channels in the cell membrane of cells lining the pancreas, respiratory tract, intestine, testes, and elsewhere (see fig. 24.2). Certain recessive mutant alleles disrupt the structure and possibly the function of the chloride channels or block its transport from the cells interior to the cell membrane. An indi vidual who inherits two such mutant alleles has cystic fi-brosis and is homozygous recessive. A person inheriting only one recessive mutant allele plus a dominant wildtype allele is a carrier and transmits the disease-causing allele in half of the gametes. A person who has two wildtype alleles is homozygous dominant for the gene and does not have or carry CF. Three genotypes are possible, but only two phenotypes, because carriers and homozy-gous dominant individuals do not have the illness.
Using logic, understanding how chromosomes and genes are apportioned into gametes in meiosis, and knowing that mutant alleles that cause cystic fibrosis are autosomal recessive, we can predict genotypes and phe-notypes of the next generation. Figure 24.5 illustrates two people who are each heterozygous for a CF-causing allele. Half of the man's sperm contain the mutant allele, as do half of the woman's eggs. Because sperm and eggs combine at random, each offspring has a
• 25% chance of inheriting two wild-type alleles (homozygous dominant, healthy, and not a carrier)
• 50% chance of inheriting a mutant allele from either parent (heterozygous and a carrier, but healthy)
• 20% chance of inheriting a mutant allele from each parent (homozygous recessive, has CF)
Genetic counselors use two tools to explain inheritance to families. A table called a Punnett square symbolizes the logic used to deduce the probabilities of particular genotypes occurring in offspring. The mother's alleles (for a particular gene) are listed atop the four boxes comprising the square, and the father's alleles are listed along the left side. Each box records the allele combinations at fertilization.
A pedigree is a diagram that depicts family relationships and genotypes and phenotypes when they are known. Circles are females and squares are males; shaded-in symbols represent people who have a trait or condition; half-shaded symbols denote carriers. Roman numerals indicate generations. Figures 24.5 and 24.6 show Punnett squares and pedigrees.
In an autosomal recessive illness, an affected person's parents are usually carriers—they do not have the illness. Or, if the phenotype is mild, a parent might be homozygous recessive and affected. In an autosomal dominant condition, an affected person typically has an affected parent. He or she need inherit only one copy of the mutant allele to have the associated phenotype; in contrast, expression of an autosomal recessive condition requires two copies of the mutant allele.
An example of an autosomal dominant condition is Huntington disease (HD). Symptoms usually begin in the late thirties or early forties and include loss of coordination, uncontrollable dancelike movements, and
Shier-Butler-Lewis: I VI. The Human Life Cycle I 24. Genetics and Genomics I I © The McGraw-Hill
Human Anatomy and Companies, 2001
Physiology, Ninth Edition
+ = wild-type allele cf = cystic fibrosis allele
For each child conceived:
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