Porth's Essentials of Pathophysiology, 4e

99

Genetic Control of Cell Function and Inheritance

C h a p t e r 5

Female Male

SUMMARY CONCEPTS

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Dd

■■ The transmission of information from one generation to the next is vested in genetic material transferred from each parent at the time of conception. ■■ Inheritance represents the likelihood of the occurrence or recurrence of a specific genetic trait. ■■ The genotype is the total sum of the genetic information that is stored in the genetic code of a person, whereas the phenotype represents the recognizable traits, physical and biochemical, associated with the genotype. ■■ Expressivity refers to the expression of a gene in the phenotype, and penetrance is the ability of a gene to express its function.The point on the DNA molecule that controls the inheritance of a particular trait is called a gene locus. ■■ Alleles are the alternate forms of a gene (one from each parent), and the locus is the position that they occupy on the chromosome.The alleles at a gene locus may carry recessive or dominant traits. ■■ Mendelian, or single-gene, patterns of inheritance include autosomal dominant and recessive traits that are transmitted from parents to their offspring in a predictable manner. A recessive trait is one expressed only when two copies (homozygous) of the recessive allele are present. Dominant traits are expressed with either homozygous or heterozygous pairing of the alleles. ■■ Polygenic inheritance, which involves multiple genes, and multifactorial inheritance, which involves multiple genes as well as environmental factors, are less predictable. ■■ A pedigree is a graphic method for portraying a family history of an inherited trait. GeneTechnology The past several decades have seen phenomenal advances in the field of genetics. These advances have included the assembly of physical and genetic maps through the Human Genome Project; the establishment of the International HapMap Project (http://hapmap. ncbi.nlm.nih.gov) to map the haplotypes of the many adjacent single-nucleotide polymorphisms in the human genome; the establishment of the 1000 Genomes Project (http://www.1000genomes.org), and the development of methods for applying the technology of these projects to the diagnosis and treatment of disease.

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DD=1/4 Dd=1/2 dd=1/4

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some human genes one of the alleles is transcriptional inactive (no RNA produced), depending on the par- ent from whom the allele is inherited. For example, an allele from the mother would be active and that from the father would be inactive. This process of gene silenc- ing was given the name genomic imprinting by Helen Crouse in 1960. It is now more commonly known as genetic imprinting . In humans, it is estimated that approximately 100 genes exhibit genetic imprinting. Evidence suggests that a genetic conflict occurs in the developing embryo: the male genome attempts to estab- lish larger offspring, whereas the female genome favors smaller offspring to conserve her energy for the current and subsequent pregnancies. It was the pathologic analysis of ovarian teratomas (tumors made up of various cell types derived from an undifferentiated germ cell) and hydatidiform moles (ges- tational tumors) that yielded the first evidence of genetic imprinting. All ovarian teratomas were found to have a 46,XX karyotype. The results of detailed chromosomal polymorphism analysis confirmed that these tumors developed without the paternally derived genome. Conversely, analysis of hydatidiform moles suggested that they were tumors of paternal origin. A related chromosomal disorder is uniparental disomy . This occurs when two chromosomes of the same number are inherited from one parent. Normally, this is not a problem except in cases where a chromo- some has been imprinted by a parent. If an allele is inactivated by imprinting, the offspring will have only one working copy of the chromosome, resulting in pos- sible problems. cheeks).The example shown is when both parents are heterozygous (dD) for the trait.The alleles carried by the mother are on the left and those carried by the father are on the top.The D allele is dominant and the d allele is recessive. The DD and Dd offspring have dimples and the dd offspring does not. FIGURE 5-11. The Punnett square showing all possible combinations for transmission of a single gene trait (dimpled