Section 28.7 Patterns of Inheritance Comprehensive Inheritance Study Guide

From Genotype to Phenotype

Genetic Composition of Human Cells:
- Every human body cell contains a full complement of DNA, which is organized and stored in $23$ pairs of chromosomes.
- Karyotype: A systematic arrangement showing these chromosome pairs in a visual format.
- Sex Chromosomes: One specific pair of chromosomes determines the biological sex of an individual. Females possess two X chromosomes ( $XX$ ), while males possess one X and one Y chromosome ( $XY$ ).

Autosomal Chromosomes: The remaining $22$ pairs of chromosomes are known as autosomes.

Genes and Protein Expression: * Each chromosome contains hundreds or thousands of genes. * Gene Expression: Genes serve as the code or instructions for the assembly of specific proteins. * Genotype: An individual’s complete genetic makeup or sequence. * Phenotype: The observable characteristics expressed by the genes, which can be physical (e.g., hair color), behavioral, or biochemical (e.g., enzyme activity).
Inheritance Patterns of Chromosomes: * Individuals inherit one chromosome from each pair—totaling $23$ chromosomes—from each parent. * This combination occurs during conception when the sperm and oocyte merge to form a diploid zygote. * Homologous Chromosomes: These are the two chromosomes within a complementary pair that contain genes for the same traits at identical locations. * Allele: A specific variation or copy of a gene inherited from one parent. * Allelic Variation Example: For the characteristic of dimples, a child might inherit an allele for dimples from the father and an allele for smooth skin (no dimples) from the mother.
Allelic Interactions: * Homozygous State: When a person has two identical alleles for a single gene. * Heterozygous State: When a person has two different alleles for a single gene. * Dominant Allele: An allele whose activity masks the expression of a non-dominant partner allele. * Recessive Allele: An allele whose expression is masked by a dominant allele; it is only expressed in the phenotype if the individual is homozygous for that allele. * Incomplete Dominance: A state where the dominance is not total, potentially resulting in an intermediate phenotype. * Codominance: A state where both alleles in a heterozygous pair are expressed simultaneously.
Complexity of Features: * Single-gene Characteristics: Features determined by one pair of genes. * Multigenic Inheritance: Features determined by the interaction of multiple genes. For example, eye color in humans is determined by at least $8$ or more genes. * Multiple Alleles: A phenomenon where more than two alleles for a specific gene exist within a population, even though an individual can only carry two. An example is the ABO blood type system, which involves three alleles: $I^A$ , $I^B$ , and $i$ .

Mendel’s Theory of Inheritance

Historical Context: * Contemporary genetics is based on the mid- $1800$ s work of Gregor Mendel, a monk who studied garden peas ( $Pisum\,sativum$ ). * Mendel discovered that physical characteristics are transmitted to subsequent generations in a discrete and predictable manner.
Mendelian Crosses and Terminology: * Pure-breeding plants: Plants that always produce offspring with the same trait when self-pollinated. * Trait: A variation of a specific characteristic (e.g., tallness vs. dwarfism for the characteristic of height). * The First-Generation (F1) Result: When crossing pure-breeding tall and dwarf plants, Mendel found all offspring were tall. He defined tallness as the dominant trait and dwarfism as recessive.
The 3:1 Phenotypic Ratio: * Mendel discovered that when F1 offspring were crossed with each other, the recessive trait reappeared in the next generation. * The observed ratio was consistently $3:1$ (three dominant phenotypes for every one recessive phenotype).
Heritable Factors: * Mendel proposed that characteristics are determined by pairs of heritable "factors" (now called genes) transmitted from each parent. * Homozygous Dominant: Carrying two dominant alleles (e.g., $TT$ ). * Homozygous Recessive: Carrying two recessive alleles (e.g., $tt$ ). * Heterozygous: Carrying one dominant and one recessive allele (e.g., $Tt$ ). These individuals are phenotypically identical to homozygous dominant individuals.
Probability and Random Segregation: * Principle of Random Segregation: During the formation of haploid gametes, the two alleles for a gene separate randomly so that each gamete has an equal chance ( $50\%$ ) of receiving either allele. * Punnett Square: A tool used to predict the likelihood of genotypes and phenotypes in offspring. * Cross between two Heterozygotes ( $Aa \times Aa$ ): * Genotypic Ratio: $1$ homozygous dominant ( $AA$ ) : $2$ heterozygous ( $Aa$ ) : $1$ homozygous recessive ( $aa$ ), or $1:2:1$ . * Phenotypic Ratio: $3$ dominant : $1$ recessive.
Principle of Independent Assortment: * One pair of alleles sorts into gametes independently of other pairs of alleles. * This means traits like seed color and plant height do not necessarily stay together unless the genes are located very close on the same chromosome.

Autosomal and X-Linked Inheritance

Autosomal Dominant Inheritance: * Occurs when the dominant allele is on one of the $22$ autosomes. * Only one copy of the faulty gene is needed for the disorder to be expressed. * Example: Neurofibromatosis type I: This disorder causes tumors in the nervous system. If one parent is heterozygous ( $Nn$ ) and the other is homozygous normal ( $nn$ ), each child has a $50\%$ chance of inheriting the disease. * Other examples: Achondroplastic dwarfism, Marfan syndrome, and Huntington’s disease.
Autosomal Recessive Inheritance: * Occurs when the disorder corresponds to the recessive phenotype. * Carrier: A heterozygous individual ( $Aa$ ) who does not display symptoms because the normal gene compensates but can pass the faulty gene to offspring. * Example: Cystic Fibrosis (CF): * Characterized by thick, tenacious mucus in the lungs and digestive tract. * Occurrence rate: Approximately $1$ in $2000$ Caucasians. * Two carrier parents have a $25\%$ chance of having an affected child ( $aa$ ) and a $50\%$ chance of having a carrier child ( $Aa$ ). * Other examples: Sickle-cell anemia, Tay–Sachs disease, and phenylketonuria.
X-Linked Dominant Inheritance: * Involves genes on the X chromosome. * Example: Vitamin D-resistant rickets: * An affected father ( $X^{affected}Y$ ) passes the disorder to $100\%$ of his daughters (who receive his X) but $0\%$ of his sons (who receive his Y). * An affected mother ( $X^{affected}X^{normal}$ ) has a $50\%$ chance of passing the disorder to any child, regardless of sex.
X-Linked Recessive Inheritance: * Much more common because females can be asymptomatic carriers. * Males: Either have the disease or are normal; they cannot be carriers because they only have one X chromosome. * Females: Can be normal, carriers, or affected. A daughter only expresses the disease if she inherits a recessive allele from both parents. * Example: Color Blindness: Affects $1$ in $20$ males but only $1$ in $400$ females. * Other examples: Hemophilia and certain forms of muscular dystrophy.

Complex Patterns and Lethal Alleles

Incomplete Dominance: * The heterozygous phenotype is an intermediate blend. * Example in humans: Hair texture. An allele for curly hair and an allele for straight hair result in wavy hair in the offspring.
Codominance in ABO Blood Types: * The $I^A$ and $I^B$ alleles are codominant. If an individual inherits both, they produce both surface antigens A and B (Type AB blood). * The allele $i$ is recessive and produces no surface antigens. Type O blood requires the genotype $ii$ . * Genotypes for Blood Types: * Type A: $I^A I^A$ or $I^A i$ . * Type B: $I^B I^B$ or $I^B i$ . * Type AB: $I^A I^B$ . * Type O: $ii$ .
Lethal Alleles: * Recessive Lethal: Faulty alleles that cause death when homozygous recessive. Example: Tay–Sachs disease, a neurological disorder where affected children usually die before age $5$ . * Dominant Lethal: Alleles where even one copy causes death. These are rare because they often cause miscarriage. However, Huntington’s disease is a dominant lethal allele that persists in the population because symptoms often do not manifest until middle age (after reproductive years).

Mutations and Chromosomal Disorders

Mutations: * A change in the DNA nucleotide sequence. * Causes: Spontaneous errors during replication, radiation, viruses, tobacco smoke, or toxic chemicals. * Impact: Can change amino acid sequences, affecting protein structure and function. Spontaneous mutations during meiosis are a common cause of miscarriages.
Chromosomal Number Abnormalities: * Nondisjunction: The failure of chromosomes to separate correctly during meiosis, leading to an incorrect number of chromosomes in gametes. * Trisomy 21 (Down Syndrome): Result of having three copies of chromosome $21$ . Incidence increases significantly in mothers over age $36$ . * Monosomy (Turner Syndrome): Result of having only one X chromosome and no second sex chromosome ( $X0$ ). The individual is female, but sterile because sexual organs do not mature.

Genetic Counseling

Role of a Genetic Counselor: * Help individuals and couples assess the risk of genetic or chromosomal disorders. * Interpret family history and explain the implications of DNA testing. * Advise on carrier status for conditions like Fragile X or Cystic Fibrosis. * Provide support for coping with diagnoses of birth defects or chromosomal disorders.
Diagnostic Testing Options: * Amniocentesis: Testing the amniotic fluid. * Chorionic Villus Sampling (CVS): Testing tissue from the placenta. * Blood tests: Used for DNA testing and carrier screening.
Professional Requirements: * A $4$ -year undergraduate degree followed by a Master of Science in Genetic Counseling. * Board certification via the American Board of Genetic Counseling.