Chromosome Inheritance and Meiosis

Chromosome Inheritance and Meiosis

• Chromosomes are inherited from both parents.
• During meiosis, maternal and paternal chromosomes are randomly separated into daughter cells.
• Crossing over, a process where homologous chromosomes exchange DNA segments, occurs before separation to increase genetic diversity.
• Each gamete (sperm or egg cell) ends up with only one set of chromosomes.
• During fertilization, a sperm and egg combine, resulting in a zygote with half of its chromosomes from the father and half from the mother.

Law of Segregation

• Each gamete receives only one copy of each gene because homologous chromosomes separate during meiosis.
• Humans have two alleles for each gene, one from each parent, which segregate during meiosis so that each gamete receives only one allele.
• Upon fertilization, offspring inherit one allele from each parent, restoring the diploid number.

Law of Independent Assortment

• Genes for different traits separate independently during gamete formation, meaning that the inheritance of one gene does not affect the inheritance of another gene if they are on different chromosomes.
• Random alignment of homologous chromosome pairs during metaphase I of meiosis leads to different combinations of maternal and paternal chromosomes in gametes.
• This law only applies to genes located on different chromosomes or genes that are far apart on the same chromosome.

Linked Genes

• Linked genes, those close together on the same chromosome, tend to be inherited together, which violates the law of independent assortment.
• Crossing over can mix up linked genes, making them behave more independently.
• The closer genes are, the less likely they are to separate; the farther apart, the more independently they behave.

Mitochondrial DNA (mtDNA) Inheritance

• mtDNA: Inherited solely from the mother.
• Sperm mitochondria are usually destroyed after fertilization.
• mtDNA is circular and resembles the genome of prokaryotic cells, supporting the endosymbiotic theory that mitochondria evolved from ancient bacteria.
• Each cell type has varying numbers of mitochondria, which influences cellular energy production.
  • Liver cells have approximately contains 1,000 to 2,000 mitochondria

Heteroplasmy and Variable Expressivity

• Heteroplasmy: A mixture of normal and mutated mtDNA within the same cell.
• Variable expressivity: Severity of a mitochondrial disorder varies among individuals due to differing proportions of mutated mtDNA.
• Since mitochondria replicate independently from nuclear DNA, some cells may have more mutated mitochondria than others.
• Higher proportions of mutated mitochondria lead to more severe symptoms of mitochondrial diseases.

Analyzing Pedigrees for Inheritance Patterns

• Pedigrees are diagrams that track the inheritance of traits through generations.
• Use the following symbols within a pedigree for each sex and their traits:
  • Use circles to represent females.
  • Use squares to represent males.
  • Shaded symbols indicate individuals affected by a disease.
  • Half-shaded symbols indicate carriers (for recessive diseases).

Autosomal Dominant Inheritance

• Every affected individual has at least one affected parent.
• There are no skipped generations.
• Males and females are equally affected.
• In families where one parent is affected, ~50% of the offspring are affected.
• Examples:
  • Familial hypercholesterolemia
  • Huntington’s disease
  • Neurofibromatosis type 1 (NF1)
  • Marfan syndrome

Autosomal Recessive Inheritance

• Unaffected carriers (heterozygous individuals) are common.
• Affected individuals (homozygous recessive) often appear in clusters.
• Consanguinity (inbreeding) is common, especially in very rare diseases.
• The trait may skip generations.
• Examples:
  • Sickle cell anemia
  • Cystic fibrosis
  • Phenylketonuria (PKU)
  • Tay-Sachs disease

X-Linked Recessive Inheritance

• Males are more frequently affected than females.
• Affected males inherit the disease from their mothers (who are carriers).
• There is no male-to-male transmission but fathers pass Y chromosome to sons.
• If an affected female exists, all of her sons are affected.
• Examples:
  • Duchenne muscular dystrophy
  • Hemophilia A and B
  • Red-green color blindness

X-Linked Dominant Inheritance

• Affected fathers pass the disease to all daughters but no sons.
• Affected mothers pass the disease to half of their children (both sons and daughters).
• Expression is often variable, especially in females.
• Examples:
  • Fragile X syndrome: Intellectual disability, with females often having milder symptoms.
  • Rett syndrome: Neurodevelopmental disorder, primarily affecting females.
  • Incontinentia pigmenti: Skin, hair, teeth, and neurological abnormalities.

Mitochondrial Inheritance

• Only inherited from the mother.
• All offspring of an affected female are affected.
• No offspring of an affected male inherit the disease.
• Symptoms often vary due to heteroplasmy.
• Examples:
  • Leber hereditary optic neuropathy (LHON)
  • Certain forms of hereditary spastic paraplegia
  • Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

X-linked Dominant Inheritance With Male Lethality

• Affected males do not survive embryonic development.
• Only females are affected.

Features of Autosomal Dominant (AD)

• Affected individuals have at least one affected parent.
• No skipping of generations (vertical transmission).
• Males and females are equally affected.
• An affected individual has a 50% chance of passing the trait to offspring.
• Unaffected individuals do not pass on the trait.

Features of Autosomal Recessive (AR)

• Parents of affected individuals are usually carriers (heterozygous, Aa) and typically unaffected.
• May skip generations.
• Males and females are equally affected.
• There is a 25% chance of affected offspring if both parents are carriers.
• More common in consanguineous (related) parents.

Features of X-Linked Recessive (XLR)

• Males are more frequently affected because they have only one X chromosome (XY).
• Affected males inherit the mutation from their mother.
• No male-to-male transmission (affected fathers do not pass it to sons).
• Females can be carriers but are usually unaffected unless homozygous.
• A carrier mother has a 50% chance of passing the mutation to sons.

Features of X-Linked Dominant (XLD)

• Males and females can be affected, but females are often less severely affected (due to X-inactivation).
• No male-to-male transmission (fathers pass the affected X to daughters, never sons).
• Affected females can transmit to both sons and daughters.

Features of Mitochondrial Inheritance

• Only inherited from the mother (since mitochondria come from the egg).
• Both males and females can be affected, but only females pass it on.
• All children of an affected mother are affected, but affected fathers do not transmit it.
• Symptoms often affect high-energy tissues like the brain, muscles, and heart.

X-linked Recessive Conditions and Carrier Mothers

• Females have two X chromosomes (XX) and one X chromosome typically compensates if the other is mutated
• Males have only one X chromosome (XY), if they inherit a mutated X it can not compensate so they develop the disease
• If the mother is a carrier, there’s a 50% chance she will pass the mutant X to her child.
• If she passes the mutant X to a son (XY): he has the disease as there is no backup X
• If she passes the mutant X to a daughter (XX): The daughter is just a carrier because she has one normal X
• Fathers with the disease cannot pass it to sons because they give their sons a Y chromosome, not an X.