Genetic Risk Assessment with Punnett Squares

Genetic Risk Assessment

• Determining inheritance patterns is crucial for calculating genetic risks within families.

Punnett Squares for Genetic Risk

• Punnett squares are a simple tool for visualizing and calculating the probability of inheriting specific alleles.
• They show potential genetic combinations in offspring, based on parental genotypes.

Autosomal Dominant Diseases

• Individuals with an autosomal dominant disease phenotype are generally assumed to have one affected allele unless specified otherwise, meaning they are heterozygous.
• Having two affected alleles (homozygous dominant) is rare and often results in lethal outcomes or more severe disease.
• The presence of just one mutated allele is usually sufficient to cause the disease
• Two mutated alleles is typically either lethal or results in a much more severe phenotype.
• Autosomal dominant diseases typically display complete penetrance, meaning if you have the allele you have the disease.
• In rare cases a person can inherit two copies of the dominant allele, which typically results in a more severe form of the disease.
• If one parent is affected (heterozygous) and the other is unaffected, each child has a 50% chance of inheriting the disease.
• If both parents are affected (heterozygous), offspring have a 25% chance of inheriting two affected alleles, potentially leading to more severe conditions.
• Ehlers-Danlos Syndrome is an example which presents with a 50% chance of the child inheriting the disease if the father is affected (heterozygous) and the mother is unaffected.

Autosomal Recessive Diseases

• Individuals must inherit two copies of the mutated gene, one from each parent, to exhibit an autosomal recessive disease.
• Those with only one mutated allele are carriers and usually asymptomatic.
• If both parents are carriers and show no symptoms, the child has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected.
• The parents' risk as carriers must be assessed to evaluate the possibility of their child being affected or being a carrier.
• With Canavan's diesease, it must first be determined the parents are carriers by assessing their parents to confirm all four grandparents are carriers.
• The probability the child presents as as affected depends on the probability that both parents are carriers and pass the mutated allele on.
• In autosomal recessive diseases, if a patient is unaffected but has a family history, there is a 2/3 chance they are a carrier
• Cystic Fibrosis is an example that presents a scenario where both parents have affected siblings, neither parent shows symptoms, and the child has a 25% chance of inheriting the disease if they both pass on the mutated allele.

X-Linked Recessive Diseases

• X-linked recessive diseases more commonly affect males because they have only one X chromosome.
• Females are usually carriers due to having two X chromosomes unless they inherit the mutated allele from both parents.
• Examples include red-green colorblindness
• If the mother is a carrier and the father is unaffected, there is a 50% chance their daughters will be carriers and a 50% chance their sons will be affected.
• If the mother has two mutant alleles, all her duaghters will be carriers and all sons will be affected.
• Duchenne Muscular Dystrophy presents an example where the mother is a carrier and the father is unaffected, there's a 50% chance the woman is a carrier herself, and a 1/4 chnace her child will have the disease.
• Males with X-linked recessive are hemizygous; they cannot be heterozygous or homozygous
• Femals can be homozygous for X-linked recessive (both X chromosomes have the mutated allele0 or heterozygous (one X-chromosome has the mutated allele, the other is normal).

X-Linked Dominant Diseases

• Both males and females can be affected, but the disease manifestations are often more severe in males.
• Rett syndrome is an example
• If the mother is heterozygous and the father is unaffected, there is a 50% chance their offspring will be affected.
• If the father is affected, all daughters will be affected because the father can only pass on the affected X chromosome to his daughters.

Mitochondrial Inheritance

• Mitochondrial DNA is inherited solely from the mother
• The father's mitochondrial DNA does not influence offspring inheritance.
• Leber hereditary optic neuropathy is an example.
• If the mother is affected, all her children will inherit the disease.
• If the mother is unaffected, none of her children will inherit the disease, regardless of the father’s status.