Genes, Chromosomes & Human Genetics

Independent Assortment: Mendel's principles state that genes assort independently during gamete formation, leading to a diverse combination of traits.
- Exception: If Mendel had studied more characters, he would have identified exceptions to his principles, such as genetic linkage.
T. H. Morgan: Utilized Drosophila melanogaster (fruit flies) to explore Mendelian genetics. His findings included:
- Genes located on the same chromosome may be inherited together (genetic linkage).
- Drosophila serves as a model organism due to the following advantages:
- Small genome (4 chromosomes)
- Shares approx. 60% of human genes
- Easy to maintain and breed with a short life span (~10 days)
- Produces a high number of offspring (up to 100 eggs daily)
- Availability of numerous mutant strains with known genetic alterations.

Wild-type: Refers to phenotypes, genotypes, or genes that are most common in a natural population.
- Dominant Traits: Example - Red eyes, normal wings in fruit flies.
- Mutant Traits: Example - Purple eyes, vestigial wings (variations of wild-type).
Genetic Linkage and Recombination:
- Crossed two true-breeding flies resulting in F1, which was heterozygous for both traits. Given Mendel's principles, this resulted in:
- Gametes Produced: 4 types.
- Phenotype Ratio: 9:3:3:1, consistent with Mendel's dihybrid crosses.
- Testcross Results: Observed recombinant phenotypes confirming linkage.

Testcross Findings:
- Expected ratio: 1:1:1:1 based on independent assortment.
- Observed more wild-type phenotypes, indicating linkage between certain genes.
Recombinant vs. Parental Phenotypes:
- Parental phenotypes were predominated. This suggests that certain genes are closely linked and less likely to assort independently.
Recombination Frequency:
- Formula:
  ext{Recombination Frequency} = rac{ ext{Number of Recombination Offspring}}{ ext{Total Offspring}} imes 100
- Map Units: Expressed in map units (mu) or centimorgans (CM), where 1 mu = 1% recombination frequency.

Chromosomal Composition:
- Females: XX (homogametic)
- Males: XY (heterogametic)
Sex-linked Genes: These genes reside on sex chromosomes and exhibit specific inheritance patterns:
- X-linked genes show different patterns in males (one allele) vs. females (two alleles).
- Example: Haemophilia is an X-linked recessive disorder, often carriers for females (due to having two Xs), while males fully express the gene if inherited.

Definition: Patterns of trait inheritance occurring via non-sex chromosomes (chromosomes 1-22).
Example: Achondroplasia (dwarfism), caused by a mutation on chromosome 4, an autosomal dominant disorder, leads to disproportionate growth due to defective cartilage development.

Cytoplasmic Inheritance: Inheritance patterns of genes located in mitochondria or chloroplasts, which are not subject to the same mechanisms as nuclear genes.
- Mitochondrial genes show uniparental inheritance, predominantly from the mother.
Genomic Imprinting:
- Expression of an allele varies based on the parent that contributed it; involves the addition of methyl groups that alter gene expression.
- Imprinting occurs in germ cells and must be reset in gametes before new imprints are established during fertilization.

Causes of Changes in Structure:
- Deletions: Loss of a chromosome segment can cause severe developmental issues.
- Duplications: Repeat a segment, leading to additional genetic material.
- Example: MECP2 duplication syndrome causes intellectual disabilities.
- Translocations: Segments moved between non-homologous chromosomes, associated with cancer.
- Inversions: Segments of chromosomes reattached but in reversed orientation, which can disrupt gene functions.

Aneuploidy: Abnormal number of chromosomes due to nondisjunction during meiosis.
- Can result in conditions like Down syndrome (trisomy 21), which arises from an extra copy of chromosome 21.
- Can be lethal early in development or lead to varying syndromes (e.g., Trisomy 18 - Edwards syndrome).
Ploidy Levels:
- Monoploidy: One set of chromosomes (n).
- Polyploidy: More than two sets of chromosomes; common in plants.

Autosomal Dominant/Recessive: The rules governing the inheritance show specific patterns based on dominance and recessiveness.
X-linked Dominant/Recessive: Confirmed through the inheritance patterns where the characteristics are traced through familial lines demonstrating gender-linked traits.
Review methods for analyzing inheritance through pedigrees, understand non-Mendelian inheritance mechanisms, and know chromosome structural variations and their impacts.