A couple wants to know the probability that their expected...

A couple wants to know the probability that their expected child will suffer from split-hand deformity, which affects the prospective father, who is indicated by an arrow in the pedigree shown. (The arrow means that he is the proband-the person in the family who first brought the disorder to the attention of medical professionals.) This trait, shown in the following photo, is rare in the population, and the prospective parents are not related to each other. a. What is the mode of inheritance of this trait? b. What is the penetrance of this trait [that is, the ratio between the number of individuals in the pedigree who display the trait (numerator), and the number of individuals you know from the pedigree must have the trait-determining genotype regardless of whether they have the trait or not (denominator)]? c. Using your answer to part (b) above, what would you tell the parents about the numerical likelihood their expected child will have split-hand deformity? d. Why is it possible that the likelihood the child will be affected is actually less than the number you just answered in part (c)? You should specify the lowest numerical likelihood that could possibly be consistent with the data.

A couple wants to know the probability that their expected child will suffer from split-hand deformity, which affects the prospective father, who is indicated by an arrow in the pedigree shown. (The arrow means that he is the proband-the person in the family who first brought the disorder to the attention of medical professionals.) This trait, shown in the following photo, is rare in the population, and the prospective parents are not related to each other.
a. What is the mode of inheritance of this trait?
b. What is the penetrance of this trait [that is, the ratio between the number of individuals in the pedigree who display the trait (numerator), and the number of individuals you know from the pedigree must have the trait-determining genotype regardless of whether they have the trait or not (denominator)]?
c. Using your answer to part (b) above, what would you tell the parents about the numerical likelihood their expected child will have split-hand deformity?
d. Why is it possible that the likelihood the child will be affected is actually less than the number you just answered in part (c)? You should specify the lowest numerical likelihood that could possibly be consistent with the data.

Key Concepts

Proband

The term proband refers to the individual in a family who first brings attention to a genetic disorder, prompting further investigation. In pedigree analysis, identifying the proband is crucial as it helps trace the inheritance pattern and assess risks for other family members. The proband's status can provide important insights into the underlying genetic mechanism and guide genetic counseling for relatives.

Autosomal Dominant Inheritance

This concept involves a pattern of inheritance where only one copy of a mutant allele is needed to express the trait. In autosomal dominant disorders, the trait tends to appear in every generation, and an affected individual has a 50% chance of passing the allele to each offspring. Pedigree charts for autosomal dominant traits typically show vertical transmission with both sexes affected equally, assuming no sex-limited expression.

Incomplete Penetrance

Incomplete penetrance means that not every individual who carries the disease-causing allele will exhibit the trait. It is defined as the proportion of individuals with the mutant genotype who display the phenotype. When calculating risks for offspring, the penetrance factor must be considered to adjust the chances of the trait being expressed, meaning that even if an individual inherits the allele, they might not display the condition.

Risk Assessment in Genetic Counseling

This concept involves calculating the likelihood that an individual will inherit a trait based on the mode of inheritance, the genotype of the parents, and any modifying factors like penetrance. In the context of autosomal dominant disorders with incomplete penetrance, the risk for offspring is determined by first calculating the probability of inheriting the allele and then applying the penetrance value to determine the actual chance of the trait manifesting.

Transcript

00:02 A couple wants to know the probability they expect the child will suffer from the split hand deformity, which affects the prospective father who is indicated by the arrow in the category shown on the board.

00:15 The arrow means that he's a proband who first brought the disease to the attention of medical professions.

00:21 So this guy, you can see the square means this is a male and shaded means that the person is affected by the disease.

00:28 So himself is affected by the disease.

00:34 And so let's take a look at this category.

00:37 So the very first question says what is the mode of inheritance? so this man's parents do not have the deformity disease.

00:46 However, his grandpa has the disease and the grandma is normal, but three out of two children they produce inherit this disease and show symptoms.

01:00 Now, although this man's father does not show any symptoms, this is probably due to the incomplete penetrance.

01:11 So the father must be a carrier.

01:13 So in this case, we can see that actually all three children produced from this grandparent couple carry this allele.

01:25 So we can probably safely say that a, the mode of inheritance is autosomal dominant and it doesn't affect one sex more than the other.

01:40 Looks like all three children of the couple were affected equally.

01:49 So autosomal dominant.

01:55 And this is because you have a high likelihood that once you inherit one allele from the father and you will show symptoms because the mother, the grandma does not have the allele.

02:08 Only the grandfather has allele, but all three kids actually inherit this allele and two of them show symptoms.

02:18 So this is most likely dominance.

02:20 Again, the father of the man most likely is a carrier.

02:26 One allele from the grandpa and one allele from grandma, but due to the incomplete penetrance, he does not show symptoms.

02:34 Now b, what is the penetrance of this trait? the ratio between the number of individuals in the pedigree who displayed the trait, which is going to be the numerator and the numbers and individual you know from the pedigree must have the trait determining genotype, regardless of they have the trait or not.

02:56 So in this case, let's say grandpa contribute a allele, keto -a, and then obviously this is dominant allele, so grandma does not have the disease.

03:11 She must have homozygous lower a.

03:14 So in all cases, their children will be heterozygous.

03:22 And although the son does not have the disease, he's also a carrier.

03:31 So he's supposed to show the symptom, but due to the incomplete penetrance, he does not show the symptom.

03:38 But he does pass this keto -a to his son, which is the man, the proband...

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