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Ch. 3 - Cell Division and Chromosome Heredity
Sanders - Genetic Analysis: An Integrated Approach 3rd Edition
Sanders3rd EditionGenetic Analysis: An Integrated ApproachISBN: 9780135564172Not the one you use?Change textbook
Chapter 3, Problem 18

The gene causing Coffin–Lowry syndrome (OMIM 303600) was recently identified and mapped on the human X chromosome. Coffin–Lowry syndrome is a rare disorder affecting brain morphology and development. It also produces skeletal and growth abnormalities, as well as abnormalities of motor control. Coffin–Lowry syndrome affects males who inherit a mutation of the X-linked gene. Most carrier females show no symptoms of the disease but a few carriers do. These carrier females are always less severely affected than males. Offer an explanation for this finding.

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Understand that Coffin–Lowry syndrome is an X-linked disorder, meaning the gene responsible for the condition is located on the X chromosome. Males (XY) have only one X chromosome, while females (XX) have two.
Recognize that males who inherit the mutated gene on their single X chromosome will express the disorder because they lack a second X chromosome to compensate for the mutation.
For females, who have two X chromosomes, one of the X chromosomes in each cell is randomly inactivated during early embryonic development. This process is called X-inactivation or lyonization, and it ensures that only one X chromosome is active in each cell.
In carrier females, some cells will have the X chromosome with the normal gene active, while others will have the X chromosome with the mutated gene active. This mosaic pattern of X-inactivation typically results in less severe symptoms compared to males, as the normal gene can partially compensate for the mutated one.
The variability in symptom severity among carrier females can be explained by the randomness of X-inactivation. If a higher proportion of cells inactivate the X chromosome with the normal gene, the symptoms may be more pronounced. Conversely, if more cells inactivate the X chromosome with the mutated gene, the symptoms will be milder or absent.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

X-Linked Inheritance

X-linked inheritance refers to the pattern of genetic transmission of genes located on the X chromosome. Males have one X and one Y chromosome, so a single mutated gene on the X chromosome will manifest as a disorder. In contrast, females have two X chromosomes, meaning they can be carriers of a mutation without showing symptoms, as the normal allele on the other X can compensate.
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X-Inactivation

Dosage Compensation

Dosage compensation is a genetic mechanism that balances the expression of X-linked genes between males and females. In mammals, one of the two X chromosomes in females is randomly inactivated (X-inactivation), leading to a situation where females express only one functional copy of X-linked genes. This results in carrier females often exhibiting milder symptoms compared to affected males, who express the mutation from their single X chromosome.
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Purpose of X Inactivation

Variable Expressivity

Variable expressivity refers to the phenomenon where individuals with the same genetic mutation exhibit different degrees of severity in symptoms. In the case of Coffin–Lowry syndrome, while most carrier females are asymptomatic or mildly affected, some may show symptoms due to factors such as the specific mutation, environmental influences, or the random nature of X-inactivation, leading to a range of phenotypic outcomes.
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Penetrance and Expressivity
Related Practice
Textbook Question

In cats, tortoiseshell coat color appears in females. A tortoiseshell coat has patches of dark brown fur and patches of orange fur that each in total cover about half the body but have a unique pattern in each female. Male cats can be either dark brown or orange, but a male cat with tortoiseshell coat is rarely produced. Two sample crosses between males and females from pure-breeding lines produced the tortoiseshell females shown.


Cross I     P: dark brown male × orange female

           F₁: orange males and tortoiseshell females

Cross II    P: orange male × dark brown female

          F₁: dark brown males and tortoiseshell females


Explain the inheritance of dark brown, orange, and tortoiseshell coat colors in cats.

Textbook Question

In cats, tortoiseshell coat color appears in females. A tortoiseshell coat has patches of dark brown fur and patches of orange fur that each in total cover about half the body but have a unique pattern in each female. Male cats can be either dark brown or orange, but a male cat with tortoiseshell coat is rarely produced. Two sample crosses between males and females from pure-breeding lines produced the tortoiseshell females shown.


Cross I     P: dark brown male × orange female

           F₁: orange males and tortoiseshell females

Cross II    P: orange male × dark brown female

           F₁: dark brown males and tortoiseshell females


Why are tortoiseshell cats female?

Textbook Question

In cats, tortoiseshell coat color appears in females. A tortoiseshell coat has patches of dark brown fur and patches of orange fur that each in total cover about half the body but have a unique pattern in each female. Male cats can be either dark brown or orange, but a male cat with tortoiseshell coat is rarely produced. Two sample crosses between males and females from pure-breeding lines produced the tortoiseshell females shown.


Cross I     P: dark brown male × orange female

           F₁: orange males and tortoiseshell females

Cross II    P: orange male × dark brown female

           F₁: dark brown males and tortoiseshell females


The genetics service of a large veterinary hospital gets referrals for three or four male tortoiseshell cats every year. These cats are invariably sterile and have underdeveloped testes. How are these tortoiseshell male cats produced? Why do you think they are sterile?

Textbook Question

Four eye-color mutants in Drosophila—apricot, brown, carnation, and purple—are inherited as recessive traits. Red is the dominant wild-type color of fruit-fly eyes. Eight crosses (A through H) are made between parents from pure-breeding lines.

Which of these eye-color mutants are X-linked recessive and which are autosomal recessive? Explain how you distinguish X-linked from autosomal heredity.

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Textbook Question

Four eye-color mutants in Drosophila—apricot, brown, carnation, and purple—are inherited as recessive traits. Red is the dominant wild-type color of fruit-fly eyes. Eight crosses (A through H) are made between parents from pure-breeding lines.

Predict F2 phenotype ratios of crosses A, B, D, and G.

Textbook Question

For each pedigree shown,

Identify which simple pattern of hereditary transmission (autosomal dominant, autosomal recessive, X-linked dominant, or X-linked recessive) is most likely to have occurred. Give genotypes for individuals involved in transmitting the trait.