Chapter 1. Chapter 6 Branched Tutorial: Pedigrees

2

Correct! Nance-Horan Syndrome is an X-linked recessive disorder characterized by congenital cataracts and dental abnormalities that is caused by a mutation in the NHS gene on chromosome Xp22 (OMIM# 302350).

Now let us proceed to answer (ii).

Incorrect. Please try again.

Incorrect.

2

Correct! If couple III-7 and III-8 had another child, the probability that the child has Nance-Horan syndrome is 1/4.

Now let us proceed to answer (iii).

Incorrect. Determine the genotypes of the parents using the pedigree and examine the possible genotypes of their progeny using a Punnett square, and then try again.

Incorrect.

2

Correct! The probability that their daughter has Nance-Horan syndrome is 1/2.

Incorrect. Use the pedigree to determine the genotype of the parents and examine the possible outcomes for their progeny using a Punnett square, and then try again.

Incorrect.

2

Correct. You will use the pattern of transmission for the disease that is summarized in the pedigree to determine whether the observed pattern of transmission is consistent with a dominant or recessive trait and whether the transmission of the disease is most likely autosomal or X-linked.

Now let’s consider another question.

Incorrect. Let’s refer to the Instant TA for guidance and try again.

Incorrect.

Instant TA

Homozygous, heterozygous, and hemizygous are terms used to describe individual genotypes. Individual genotypes can be deduced based on the pattern of inheritance, but you are first identifying the transmission pattern for the trait that is observed for the entire family.

Patterns of inheritance are described as either dominant or recessive and as either autosomal or sex-linked. Dominant refers to a phenotype that is identical in heterozygous individuals and homozygotes. Recessive refers to a phenotype that is only observed in the homozygote. A sex-linked trait is determined by a gene located on a sex chromosome (X or Y).and may be inherited disproportionately by one sex. An autosomal trait is determined by a gene located on an autosomal (non-sex) chromosome. and should be inherited approximately equally by progeny of each sex. Which pattern best describes the pedigree in this problem?

You can test your answer by determining (i) the genotypes of individuals in the pedigree based on your chosen pattern of inheritance; and (ii) whether matings between individuals with these genotypes would produce a pattern consistent with your hypothetical mode of inheritance.

Instructions

Read the problem carefully and note the following:

    •What information is provided for you?
    •What information are you asked to provide or determine to solve the problem?

You will answer a series of multiple choice questions to help you identify the information and concepts that you need to answer problems (i)-(iii). The Instant TA will be available on-demand to assist you and as a resource if you answer a question incorrectly.

2

Great job! Five generations of hereditary information is included in the pedigree and there are 6 individuals who have been diagnosed with Nance-Horan syndrome, all of whom are male. Now let’s answer a second question.

Incorrect. Let’s consult the Instant TA for guidance and try again.

Incorrect.

Instant TA

Examine the provided pedigree, then use the observed pattern of inheritance to select the correct answer. You may want to consider the following points as you review the pedigree:
    Males are represented by squares; females are represented by circles.
    Persons unaffected by the disease are shown as open symbols; persons affected by the disease are shown as filled
    Generations are designated using Roman numerals and children are connected to their parents using a vertical line.

2

Correct. Nance-Horan syndrome is not observed in either generation I or V. Recessive traits often skip generations.

Now let’s answer problem (i).

Incorrect. Let’s refer to the Instant TA for guidance and try again.

Incorrect.

Instant TA

Dominant and recessive traits produce different patterns in a pedigree.
     Individuals expressing a dominant trait will have at least one affected parent who also expresses the trait.
     Individuals expressing a recessive trait may have unaffected parents, if the parents are heterozygous for the trait, so recessive traits may skip a generation.
     Heterozygous parents will express the dominant phenotype associated with a gene.
     Examine the pattern of inheritance on the provided pedigree and determine whether Nance-Horan syndrome is inherited as a dominant or recessive trait.

2

Great job! Nance-Horan Syndrome is an X-linked recessive disorder characterized by congenital cataracts and dental abnormalities that is caused by a mutation in the NHS gene on chromosome Xp22 (OMIM# 302350).

Now let us proceed to answer Problem (ii).

Incorrect. Let’s consult the Instant TA for guidance, then try again.

Incorrect.

Instant TA

To determine the pattern of inheritance exhibited for Nance-Horan disease by this family, you must determine whether the disease is (i) inherited as a dominant or recessive trait; and (ii) transmitted on an autosome or sex chromosome.
     An individual expressing a dominant trait will have at least one parent affected by the trait.
     An individual expressing a recessive trait may have unaffected parents.
     A disease that is transmitted on an autosome will be inherited by a roughly equal number of males and females.
     A disease transmitted on a sex chromosome may be inherited by more members of one sex than the other, depending on whether the gene is on the X- or Y-chromosome and whether the disease is expressed as a dominant or recessive trait.

Construct Punnett squares comparing the pattern of inheritance exhibited by your two most likely choices. Which pattern best fits what is observed on the pedigree?

2

Correct. Both individuals are males that are hemizygous for the disease causing allele.

Now let’s try to answer a second question.

Incorrect. Let’s consult the Instant TA, then try again.

Incorrect.

Instant TA

Individuals IV-5 and IV-7 are two of the three male children born to the couple III-7 and III-8. Both individuals IV-5 and IV-7 have Nance-Horan syndrome, but their brother is not affected. Also, neither of their parents have Nance-Horan syndrome. Use what you know about patterns of inheritance to deduce the genotypes of individuals IV-5 and IV-7.
     Nance-Horan syndrome is inherited as an X-linked recessive trait.
     Males inherit their X-chromosomes from their mothers.
     Both IV-5 and IV-7 are males with Nance-Horan syndrome, so they must carry the disease-causing allele on their X chromosome.

What does the hemizygous genotype of boys IV-5 and IV-7 and their unaffected brother indicate about the genotype of their mother, who does not have Nance-Horan syndrome?

2

Correct. The woman III-7 is heterozygous for the disease-causing allele, which is found on the X-chromosome.

Now let’s try to answer Problem (ii).

Incorrect. Let’s consult the Instant TA for guidance, then try again.

Incorrect.

Instant TA

Individual III-7 is a woman who has two sons with Nance-Horan syndrome and one son who does not have the disease. If sons inherit their X-chromosome from their mothers, what is the woman’s (III-7) genotype?

Construct a Punnett square showing the possible genotypes of the offspring of an unaffected male and a female carrier to confirm the inheritance pattern seen for this family.

2

Great job! If couple III-7 and III-8 have another child, the probability is 1/4 that the child has Nance-Horan syndrome. The genotype fulfilling this condition is X^dY, so the affected child must also be a male.

Now let us proceed to answer problem (iii).

Incorrect. Let’s consult the Instant TA for guidance, then try again.

Incorrect.

Instant TA

For an X-linked recessive trait, an unaffected female who is a carrier of a disease will pass the disease on to about half of her sons. If she mates with an unaffected male, none of her daughters will inherit the disease, but about half of her daughters will be carriers.

Use a Punnett square to confirm this pattern of inheritance and determine the probability that children of the couple will have Nance-Horan syndrome.

2

Correct. III-2 is a hemizygous male carrying the disease-causing allele and III-8 is a hemizygous male carrying the normal allele.

Now let’s answer a second multiple choice question.

Incorrect. Let’s consult the Instant TA for guidance, then try again.

Incorrect.

Instant TA

For an X-linked recessive trait, an unaffected male will have an X chromosome carrying a normal allele. An affected male will have an X chromosome carrying the disease-causing allele. Hemizygous describes a genotype where the individual possesses a single allele at a locus. Males are hemizygous for X-linked loci because their cells possess a single X chromosome.

Use a Punnett square to compare differences in the pattern of inheritance obtained when each of these males mates with a carrier for Nance-Horan syndrome.

2

Correct! One-half of their children would be expected to have Nance-Horan syndrome, with both male and female children affected.

Incorrect. Let’s consult the Instant TA for guidance, then try again.

Incorrect.

Instant TA

Human males possess a single X- chromosome and are said to be hemizygous for X-linked traits. For an X-linked recessive trait, an unaffected male will have an X chromosome carrying a normal allele. An affected male will have an X chromosome carrying the disease-causing allele. Females possess two X chromosomes, so an unaffected female may be either homozygous for the normal allele or heterozygous, while the affected female will carry the disease-causing allele on both X chromosomes. The heterozygous female may act as a carrier, passing the disease-causing allele on to both female and male progeny in the next generation.

Use a Punnett square to compare differences in the pattern of inheritance obtained when each of these males (III-2 and III-8) mates with a carrier for Nance-Horan syndrome.

2

Correct! If III-2 and III-7 have a daughter, there is probability of 1/2 that the girl has Nance-Horan syndrome.

Incorrect. Let’s consult the Instant TA for guidance, then try again.

Incorrect.

Instant TA

In Problem (ii) individual III-7, a female carrier of Nance-Horan syndrome, had three children with individual III-8, an unaffected male. Two of their sons inherited an X chromosome carrying the disease-causing allele from their mother, so they have Nance-Horan syndrome. What is the chance that a daughter of this couple suffers from Nance-Horan syndrome?

Since individual III-8 does not have the disease, his genotype is designated XY. Each child of III-8 and III-7 (XX^d) will have one of four equally likely genotypes, as shown by the Punnett square above. Of these genotypes, only one combination of gametes results in the inheritance of Nance-Horan syndrome: a male with genotype X^dY. Thus, there is 1/4 chance that couple III-7 and III-8 will have a child with Nance-Horan syndrome, but no daughters will have the disease.

The question “If individual III-2 and III-7 have a daughter, what is the probability that the child has Nance-Horan syndrome?” has a different answer. First, the birth of a daughter restricts the number of possible outcomes from four to two, since only genotypes with two X chromosomes would be genetically female. Second, III-2 suffers from Nance-Horan syndrome, unlike the other father, individual III-8. To determine the probability for a daughter of this couple to have the disease, the number of possible genotypes producing an affected female is divided by the total number of genotypes resulting in a daughter.

Construct a Punnett square showing the possible genotypes of a daughter of III-2 and III-7 and determine the fraction of those genotypes that result in Nance-Horan syndrome.