Genetic Patterns of InheritanceReviewing the Genetics Behind Huntington's Disease and Other Inherited Disorders
It’s a good idea to review patterns of inherited diseases when preparing for ABIM exams - the American Board of Internal Medicine (ABIM) board exam or recertification examinations.
Here are the most common ones along with Punnett square examples to show the probability of each combination of parental genes.
One parent transmits an abnormal gene to an offspring. In some cases, the condition may result from a new mutation with no history of the disorder in the family.
In autosomal dominant disorders, one can predict what percentage of the children will be affected by knowing the status of both parents.
So in the chart below, in Example #1, if one parent is homozygous for the abnormal gene (WW) all of the children will have the disorder regardless of the genetic makeup of the partner.
If both parents are heterozygous (Example 2), 75% of the children will be affected.
If one is heterozygous and the other does not have the abnormal gene (Example 3), 50% of the children will be affected.
Figures. Autosomal Dominant Example; Autosomal Dominant vs. Recessive
Huntington’s Disease is an example of an autosomal dominant disorder where its appearance in the children of an affected parent may be variable.
The disease results when one parent passes on a gene that has an excessive number of three base pair sequences occurring in a row (Cytosine-Adenine-Guanine).
Normal people have up to 26 triple repeats.
Those with 27-35 will not have the disease but one of their children may.
People with 36-39 may or may not develop the disease.
If so, it is at a later age.
Those with 40 or more triple repeats will definitely develop the disease.
The more triple repeats they have, the earlier the disease will appear.
The number of repeats can get larger when passed on to a child but only by the father.
In-vitro fertilization can identify whether or not the child will develop Huntington’s disease by examining the number of repeats in a single cell.
In autosomal recessive inheritance, the disease is not fully expressed in children unless each parent contributes a copy of the abnormal gene.
When both parents are heterozygous, 25% of the children will have the disease, and 50%, like their parents, will have the trait (heterozygous); 25% will have neither the disease nor the trait.
Sickle cell disease and cystic fibrosis are examples of autosomal recessive disorders. Heterozygous persons may have mild symptoms compared to those who are homozygous. Sickle Cell trait is such an example.
Figure. Autosomal Recessive
X-linked dominant disorders are caused by a genetic mutation on an X chromosome.
In females, a mutation in one of the two X chromosomes is sufficient to cause the disorder.
In males, a mutation in the only X chromosome causes the disorder.
Fathers cannot pass x-linked traits to their sons, since they contribute only the Y chromosome.
Fragile X syndrome is an example of an X-linked dominant disorder.
Figure. X-linked Dominant Chart, Affected Father and Affected Mother
X-linked Recessive disorders are also caused by mutations in genes on the X-chromosome.
In males, one copy of the gene is sufficient to cause the disease since males have only one X-chromosome.
In females, a mutation would have to occur in both X chromosomes to cause the disorder, thus it is rarely observed in females.
In X-linked recessive disorders, fathers cannot pass their trait on to their sons.
Hemophilia is the most well- known example of an X-linked recessive disorder.
Figure. X-linked Recessive Chart
Exam Review Tip:
Y-linked, codominant, mitochondrial disorders are less common and not likely to be asked on the ABIM exam.
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