Chapter 13

Chromosomal Theory of Inheritance: Proposed by Carl Correns (1900) and later refined by Walter Sutton (1902).
- Carl Correns: Suggested the central role of chromosomes in inheritance.
- Walter Sutton: Led the development of the chromosomal theory based on meiosis observations, where similar chromosomes pair with one another.

Exceptions to Mendelian Genetics: Inheritance patterns that do not conform to Mendel's laws include sex-linked traits and mitochondrial inheritance.

Genetic Mapping: Early geneticists like Alfred Sturtevant used genetic recombination patterns to estimate distances between genes.
- Crossover Effects: If crossover occurs, parental alleles are recombined to form recombinant gametes, influencing genetic mapping.
- Distance Estimates: Reflected by recombination frequencies, measured in map units (1% recombination = 1 map unit = 1 centimorgan (cM)).

Human Chromosomes: Humans have a total of 46 chromosomes, consisting of 22 pairs of autosomes (non-sex chromosomes) and 1 pair of sex chromosomes (X and Y).
X and Y Chromosome Functions:
- The Y chromosome is highly condensed with fewer genes compared to the X chromosome.
- Sex Linkage: Many traits are linked to the X chromosome, leading to conditions like red-green color blindness and hemophilia, which primarily affect males.
- In females, one X chromosome is randomly inactivated, forming a Barr body, allowing female heterozygotes to be genetic mosaics (e.g., calico cats).

Human Genetic Studies: Genetic mapping techniques identify associations between genetic markers and human traits or disorders.
Mitochondrial and Chloroplast Genes: These genes do not follow typical Mendelian inheritance patterns as they are often inherited from one parent, primarily the mother.
- Example: Maternal inheritance of mitochondrial traits.

Examples of X-linked recessive alleles:
- Color Blindness: Difficulty distinguishing colors due to anomalies in photopigments.
- Hemophilia: A disorder characterized by defective blood-clotting factors, more common in males due to X-linked inheritance.

Genomic Imprinting: Differential expression of alleles depending on parent contribution, leading to conditions like Angelman syndrome (maternal allele) and Prader-Willi syndrome (paternal allele).
Mendelian Disorders: Some disorders exhibit clear dominant or recessive patterns, e.g., juvenile glaucoma (dominant) and albinism (recessive).
Nondisjunction: Refers to the failure of homologous chromosomes to separate properly during meiosis resulting in aneuploidy, such as Down syndrome (trisomy 21).

Recombination Frequency Measurement: Used to calculate genetic distances and create linkage maps by analyzing offspring phenotypes from test crosses.
Example of Mapping: The F1 generation produces different recombinant offspring, illustrating genetic distances between loci (e.g., 18% recombination frequency indicates 18 cM).

Three-point crosses allow geneticists to track recombination events across multiple loci, determining gene orders based on frequencies of hybrid offspring.

Genome-Wide Association Studies (GWAS): Used to identify SNPs that correlate with diseases. Requires massive data from population levels, and although associations are found, they don't imply causality.
Phenotype-wide Association Studies (PheWAS): Explores known genetic variants and their associations with various phenotypes based on large datasets.