Question

A boy with Klinefelter syndrome \((47, \mathrm{XXY})\) is born to a mother who is phenotypically normal and a father who has the X-linked skin condition called anhidrotic ectodermal dysplasia. The mother's skin is completely normal with no signs of the skin abnormality. In contrast, her son has patches of normal skin and patches of abnormal skin. (a) Which parent contributed the abnormal gamete? (b) Using the appropriate genetic terminology, describe the meiotic mistake that occurred. Be sure to indicate in which division the mistake occurred. (c) Using the appropriate genetic terminology, explain the son's skin phenotype.

Short answer

Answer: The father contributed the abnormal gamete, and the meiotic mistake that occurred in the development of the child is called "nondisjunction" during meiosis II, resulting in a sperm cell with both X and Y chromosomes. This led to a child with a 47, XXY genotype and an X-linked skin condition due to mosaicism.

Step-by-step solution

(a) Determining the Parent Contributing the Abnormal Gamete

Since the mother is phenotypically normal and the father has the X-linked skin condition, the abnormal X chromosome carrying the skin anomaly must have come from the father. The mother contributed one normal X chromosome, and the father contributed both the abnormal X chromosome (with the skin condition allele) and the Y chromosome, which caused the child to have Klinefelter syndrome, i.e., 47, XXY.

(b) Description of the Meiotic Mistake

The meiotic mistake that occurred is called "nondisjunction". Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during meiosis I or meiosis II. In this case, nondisjunction occurred during meiosis II when the sister chromatids of the father's X chromosome failed to separate. As a result, one of the sperm cells had both the X and Y chromosomes (a "XY" sperm), while another sperm cell had no sex chromosomes. The XY sperm then fertilized a normal egg with an X chromosome, which led to a child with a 47, XXY genotype.

(c) Explanation of the Son's Skin Phenotype

The son's skin phenotype is a result of "mosaicism", which means that the child has a mixture of two or more genetically distinct cell populations in his body. In this case, the son's cells either have the normal X chromosome from the mother (referred to as X-inactivation) or the abnormal X chromosome with the skin condition allele from the father, causing patches of normal skin and patches of abnormal skin. Mosaicism occurs in early embryonic development when the X-chromosomes randomly inactivate in different cells, leading to a varying degree of expression for the X-linked genes in different cells.

Key concepts

Nondisjunction

Nondisjunction is a critical concept in genetics, especially when discussing chromosomal disorders such as Klinefelter syndrome. It refers to the improper separation of chromosomes during the cell division processes of meiosis I or meiosis II. Under normal circumstances, chromosomes should segregate evenly, so that each gamete, which is a sperm or an egg cell, receives only one complete set of chromosomes.

However, if nondisjunction occurs, as it did with the father in the exercise, a gamete may end up with an extra chromosome or missing one. When such a gamete with an abnormal number of chromosomes fertilizes a normal gamete, it can lead to an embryo with a chromosomal anomaly like Klinefelter syndrome (47, XXY). This process is a key aspect in understanding genetic conditions that arise not from gene mutations, but from chromosomal abnormalities at the cellular level.

X-linked Genetic Conditions

X-linked genetic conditions are disorders caused by mutations in genes on the X chromosome. In the example of anhidrotic ectodermal dysplasia, which is X-linked, males are more severely affected because they have only one X chromosome. If their single X chromosome carries the mutated gene, they will present with the disorder, as there is no second X to offset the effect.

In females, who have two X chromosomes, a mutation in one X may not cause the disorder because the normal allele on the other X can compensate. This compensation is crucial to understanding why the mother in the exercise, despite likely carrying the ectodermal dysplasia allele, does not exhibit the condition, while her son, with one X chromosome from his father carrying the mutation, does show signs of the disorder in patches.

Mosaicism

Mosaicism involves the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg. In the context of the exercise, the son with Klinefelter syndrome displays mosaicism, which explains the patches of normal and abnormal skin.

This occurs due to the random occurrence of X-inactivation during embryonic development, where either the mother's normal X or the father's abnormal X chromosome is inactivated in different cells. The result is a person with varied expression of X-linked genes, which in this case manifests physically in the skin of the affected individual. Mosaicism is an essential concept to grapple with the varied phenotypes that can occur even within a single genetic condition.

X-inactivation

X-inactivation plays a pivotal role in the genetic expression of X-linked traits, particularly in females. Normally, females possess two X chromosomes, but to prevent an overdose of X-linked gene products, one of these X chromosomes is randomly inactivated in each cell. This process occurs early in embryonic development and is permanent for those cells and their descendants.

The patches of skin on the son from the exercise are a clear example of how X-inactivation can lead to different phenotypes being expressed in different areas of the body, despite the same genetic makeup. Understanding X-inactivation sheds light on the variance we observe among individuals with the same genetic condition, especially for X-linked traits.

Meiosis II

Meiosis II is one of the two stages of meiosis, a specialized type of cell division that produces gametes for sexual reproduction. It follows meiosis I and is similar to mitosis, where sister chromatids – the identical copies formed by DNA replication – are separated. However, when nondisjunction occurs in meiosis II, as seen in the father's sperm that led to the Klinefelter syndrome, sister chromatids do not separate properly.

This error results in gametes that contain an abnormal number of chromosomes, contributing to disorders like Klinefelter syndrome. Comprehending meiosis II is vital for understanding how genetic variations and disorders are transmitted through generations, particularly those stemming from errors in gamete formation.