CASE STUDY|One foot or another In humans the HOXD homeotic gene cluster plays a critical role in limb development. In one large family, 16 of 36 members expressed one of two dominantly inherited malformations of the feet known as rocker bottom foot (CVT) or claw foot (CMT). One individual had one foot with CVT and the other with CMT. Genomic analysis identified a single missense mutation in the HOXD10 gene, resulting in a single amino acid substitution in the homeodomain of the encoded transcription factor. This region is crucial for making contact and binding to the target genes controlled by this protein. All family members with the foot malformations were heterozygotes; all unaffected members were homozygous for the normal allele. Given that affected heterozygotes carry one normal allele of the HOXD10 gene, how might a dominant mutation in a gene encoding a transcription factor lead to a developmental malformation?

Question

Want to see more full solutions like this?

Answer 1

Textbook Question

Chapter 20, Problem 1CS

CASE STUDY|One foot or another

In humans the HOXD homeotic gene cluster plays a critical role in limb development. In one large family, 16 of 36 members expressed one of two dominantly inherited malformations of the feet known as rocker bottom foot (CVT) or claw foot (CMT). One individual had one foot with CVT and the other with CMT. Genomic analysis identified a single missense mutation in the HOXD10 gene, resulting in a single amino acid substitution in the homeodomain of the encoded transcription factor. This region is crucial for making contact and binding to the target genes controlled by this protein. All family members with the foot malformations were heterozygotes; all unaffected members were homozygous for the normal allele.

Given that affected heterozygotes carry one normal allele of the HOXD10 gene, how might a dominant mutation in a gene encoding a transcription factor lead to a developmental malformation?

Expert Solution & Answer

Summary Introduction

Case summary:

In this case16 of 36 members of a large family were found to have one of the two malformations of the feet called claw foot (CMT) or rocker bottom foot (CVT). Even one individual had both the affected foot, one with CVT and the other with CMT.

Characters in the case:

A family with varying foot malformations.

Adequate information:

HOXD homeotic gene cluster in humans is involved in limb development. A single missense mutationhas been recognized in the HOXD10 gene by genomic analysis. As a result, substitution of a single amino acid took place in the homeodomain of the encoded transcription factor. This region is important as it makes contact and binds to the target genes directed by this protein.

To determine:

A dominant mutation in a gene encoding a transcription factor lead to a developmental malformation.

Given information:

The affected heterozygotes carry one normal allele of the HOXD10 gene, while all unaffected members are homozygous and carry normal alleles.

Explanation of Solution

HOX gene cluster has a role in the development of limb and is responsible to give protein products that act as transcription factors. Four clusters of HOXD gene are present: HOXA, HOXC, HOXB, and HOXD. Thus, combination of 2 to 4 HOX genes form particular structures. Therefore, mutations in only one HOX gene do not result into complete transformation.

HOXD10 belongs to a cluster of HOXD genes located on chromosome 2. Mutations in this gene causes congenital vertical talus (rocker bottom foot or claw foot). A missense mutation was observed in HOXD10 gene, in which substitution of a single nucleotide in the dominant allele might result in a codon coding for different amino acid.

Despite of one normal allele, the person get disease as the mutated allele suppresses the expression of normal allele, leading to severe consequences. This results into the failure of the production of required transcription factor, due to which developmental malformation happened.

Conclusion

Therefore, it can be concluded that missense mutation in a gene that encodes for a transcription factorresults into developmental malformation, even if one normal allele is present.

Want to see more full solutions like this?

Subscribe now to access step-by-step solutions to millions of textbook problems written by subject matter experts!

Students have asked these similar questions

Susan’s grandfather was deaf, and passed down a hereditary form of deafness within Susan’s family as shown in Figure Q19–12.A. Is this mutation most likely to be dominant or recessive?B. Is it carried on an autosome or a sex chromosome? Why?C. A complete SNP analysis has been done for all of the 11 grandchildren (4 affected, and 7 unaffected). In comparing these 11 SNP results, how long a haplotype block would you expect to find around the critical gene? How might you detect it?

Researchers have exploited Minute mutations in orderto study the phenotypes associated with recessive lethal mutations (l−) that decrease the rate of cell divisionand thus make only very tiny homozygous mutant clones that are difficult to analyze. Many differentstrains of Drosophila carry dominant loss-of-functionMinute (M) mutations in a variety of genes encodingribosomal protein subunits. The M genes are haploinsufficient; flies with only one wild-type M+ gene copyhave a slower pace of cell division, and thus prolongeddevelopment and subtle morphological abnormalities.To circumvent the tiny clone problem, researchersgenerate GFP-marked homozygous l−/ l− clones thatare also M+/ M+, in flies that are l−/ l+ and M−/ M+.The loss of the Minute mutation only in cells withinthe clone gives the l−/ l− cells a growth advantageover their neighbors, enabling the mutant clone togrow large enough to study. Diagram chromosomesthat could be used to generate such clones

Synpolydactyly is an abnormality characterized by webbing between partially or completely duplicated fingers or toes (Figure 18.15). The same mutations that cause the human phenotype give rise to a similar phenotype in mice. In what family of genes do you think these mutations occur?

Answer 2

Textbook Question

Chapter 20, Problem 1CS

CASE STUDY|One foot or another

In humans the HOXD homeotic gene cluster plays a critical role in limb development. In one large family, 16 of 36 members expressed one of two dominantly inherited malformations of the feet known as rocker bottom foot (CVT) or claw foot (CMT). One individual had one foot with CVT and the other with CMT. Genomic analysis identified a single missense mutation in the HOXD10 gene, resulting in a single amino acid substitution in the homeodomain of the encoded transcription factor. This region is crucial for making contact and binding to the target genes controlled by this protein. All family members with the foot malformations were heterozygotes; all unaffected members were homozygous for the normal allele.

Given that affected heterozygotes carry one normal allele of the HOXD10 gene, how might a dominant mutation in a gene encoding a transcription factor lead to a developmental malformation?

Expert Solution & Answer

Summary Introduction

Case summary:

In this case16 of 36 members of a large family were found to have one of the two malformations of the feet called claw foot (CMT) or rocker bottom foot (CVT). Even one individual had both the affected foot, one with CVT and the other with CMT.

Characters in the case:

A family with varying foot malformations.

Adequate information:

HOXD homeotic gene cluster in humans is involved in limb development. A single missense mutationhas been recognized in the HOXD10 gene by genomic analysis. As a result, substitution of a single amino acid took place in the homeodomain of the encoded transcription factor. This region is important as it makes contact and binds to the target genes directed by this protein.

To determine:

A dominant mutation in a gene encoding a transcription factor lead to a developmental malformation.

Given information:

The affected heterozygotes carry one normal allele of the HOXD10 gene, while all unaffected members are homozygous and carry normal alleles.

Explanation of Solution

HOX gene cluster has a role in the development of limb and is responsible to give protein products that act as transcription factors. Four clusters of HOXD gene are present: HOXA, HOXC, HOXB, and HOXD. Thus, combination of 2 to 4 HOX genes form particular structures. Therefore, mutations in only one HOX gene do not result into complete transformation.

HOXD10 belongs to a cluster of HOXD genes located on chromosome 2. Mutations in this gene causes congenital vertical talus (rocker bottom foot or claw foot). A missense mutation was observed in HOXD10 gene, in which substitution of a single nucleotide in the dominant allele might result in a codon coding for different amino acid.

Despite of one normal allele, the person get disease as the mutated allele suppresses the expression of normal allele, leading to severe consequences. This results into the failure of the production of required transcription factor, due to which developmental malformation happened.

Conclusion

Therefore, it can be concluded that missense mutation in a gene that encodes for a transcription factorresults into developmental malformation, even if one normal allele is present.

Want to see more full solutions like this?

Subscribe now to access step-by-step solutions to millions of textbook problems written by subject matter experts!

Answer 3

Textbook Question

Chapter 20, Problem 1CS

CASE STUDY|One foot or another

In humans the HOXD homeotic gene cluster plays a critical role in limb development. In one large family, 16 of 36 members expressed one of two dominantly inherited malformations of the feet known as rocker bottom foot (CVT) or claw foot (CMT). One individual had one foot with CVT and the other with CMT. Genomic analysis identified a single missense mutation in the HOXD10 gene, resulting in a single amino acid substitution in the homeodomain of the encoded transcription factor. This region is crucial for making contact and binding to the target genes controlled by this protein. All family members with the foot malformations were heterozygotes; all unaffected members were homozygous for the normal allele.

Given that affected heterozygotes carry one normal allele of the HOXD10 gene, how might a dominant mutation in a gene encoding a transcription factor lead to a developmental malformation?

Expert Solution & Answer

Summary Introduction

Case summary:

In this case16 of 36 members of a large family were found to have one of the two malformations of the feet called claw foot (CMT) or rocker bottom foot (CVT). Even one individual had both the affected foot, one with CVT and the other with CMT.

Characters in the case:

A family with varying foot malformations.

Adequate information:

HOXD homeotic gene cluster in humans is involved in limb development. A single missense mutationhas been recognized in the HOXD10 gene by genomic analysis. As a result, substitution of a single amino acid took place in the homeodomain of the encoded transcription factor. This region is important as it makes contact and binds to the target genes directed by this protein.

To determine:

A dominant mutation in a gene encoding a transcription factor lead to a developmental malformation.

Given information:

The affected heterozygotes carry one normal allele of the HOXD10 gene, while all unaffected members are homozygous and carry normal alleles.

Explanation of Solution

HOX gene cluster has a role in the development of limb and is responsible to give protein products that act as transcription factors. Four clusters of HOXD gene are present: HOXA, HOXC, HOXB, and HOXD. Thus, combination of 2 to 4 HOX genes form particular structures. Therefore, mutations in only one HOX gene do not result into complete transformation.

HOXD10 belongs to a cluster of HOXD genes located on chromosome 2. Mutations in this gene causes congenital vertical talus (rocker bottom foot or claw foot). A missense mutation was observed in HOXD10 gene, in which substitution of a single nucleotide in the dominant allele might result in a codon coding for different amino acid.

Despite of one normal allele, the person get disease as the mutated allele suppresses the expression of normal allele, leading to severe consequences. This results into the failure of the production of required transcription factor, due to which developmental malformation happened.

Conclusion

Therefore, it can be concluded that missense mutation in a gene that encodes for a transcription factorresults into developmental malformation, even if one normal allele is present.

Want to see more full solutions like this?

Subscribe now to access step-by-step solutions to millions of textbook problems written by subject matter experts!

Answer 4

Textbook Question

Chapter 20, Problem 1CS

CASE STUDY|One foot or another

In humans the HOXD homeotic gene cluster plays a critical role in limb development. In one large family, 16 of 36 members expressed one of two dominantly inherited malformations of the feet known as rocker bottom foot (CVT) or claw foot (CMT). One individual had one foot with CVT and the other with CMT. Genomic analysis identified a single missense mutation in the HOXD10 gene, resulting in a single amino acid substitution in the homeodomain of the encoded transcription factor. This region is crucial for making contact and binding to the target genes controlled by this protein. All family members with the foot malformations were heterozygotes; all unaffected members were homozygous for the normal allele.

Given that affected heterozygotes carry one normal allele of the HOXD10 gene, how might a dominant mutation in a gene encoding a transcription factor lead to a developmental malformation?

Expert Solution & Answer

Summary Introduction

Case summary:

In this case16 of 36 members of a large family were found to have one of the two malformations of the feet called claw foot (CMT) or rocker bottom foot (CVT). Even one individual had both the affected foot, one with CVT and the other with CMT.

Characters in the case:

A family with varying foot malformations.

Adequate information:

HOXD homeotic gene cluster in humans is involved in limb development. A single missense mutationhas been recognized in the HOXD10 gene by genomic analysis. As a result, substitution of a single amino acid took place in the homeodomain of the encoded transcription factor. This region is important as it makes contact and binds to the target genes directed by this protein.

To determine:

A dominant mutation in a gene encoding a transcription factor lead to a developmental malformation.

Given information:

The affected heterozygotes carry one normal allele of the HOXD10 gene, while all unaffected members are homozygous and carry normal alleles.

Explanation of Solution

HOX gene cluster has a role in the development of limb and is responsible to give protein products that act as transcription factors. Four clusters of HOXD gene are present: HOXA, HOXC, HOXB, and HOXD. Thus, combination of 2 to 4 HOX genes form particular structures. Therefore, mutations in only one HOX gene do not result into complete transformation.

HOXD10 belongs to a cluster of HOXD genes located on chromosome 2. Mutations in this gene causes congenital vertical talus (rocker bottom foot or claw foot). A missense mutation was observed in HOXD10 gene, in which substitution of a single nucleotide in the dominant allele might result in a codon coding for different amino acid.

Despite of one normal allele, the person get disease as the mutated allele suppresses the expression of normal allele, leading to severe consequences. This results into the failure of the production of required transcription factor, due to which developmental malformation happened.

Conclusion

Therefore, it can be concluded that missense mutation in a gene that encodes for a transcription factorresults into developmental malformation, even if one normal allele is present.

Want to see more full solutions like this?

Subscribe now to access step-by-step solutions to millions of textbook problems written by subject matter experts!

Answer 5

Textbook Question

Answer 6

Textbook Question

Answer 7

Expert Solution & Answer

Summary Introduction

Case summary:

In this case16 of 36 members of a large family were found to have one of the two malformations of the feet called claw foot (CMT) or rocker bottom foot (CVT). Even one individual had both the affected foot, one with CVT and the other with CMT.

Characters in the case:

A family with varying foot malformations.

Adequate information:

HOXD homeotic gene cluster in humans is involved in limb development. A single missense mutationhas been recognized in the HOXD10 gene by genomic analysis. As a result, substitution of a single amino acid took place in the homeodomain of the encoded transcription factor. This region is important as it makes contact and binds to the target genes directed by this protein.

To determine:

A dominant mutation in a gene encoding a transcription factor lead to a developmental malformation.

Given information:

The affected heterozygotes carry one normal allele of the HOXD10 gene, while all unaffected members are homozygous and carry normal alleles.

Explanation of Solution

HOX gene cluster has a role in the development of limb and is responsible to give protein products that act as transcription factors. Four clusters of HOXD gene are present: HOXA, HOXC, HOXB, and HOXD. Thus, combination of 2 to 4 HOX genes form particular structures. Therefore, mutations in only one HOX gene do not result into complete transformation.

HOXD10 belongs to a cluster of HOXD genes located on chromosome 2. Mutations in this gene causes congenital vertical talus (rocker bottom foot or claw foot). A missense mutation was observed in HOXD10 gene, in which substitution of a single nucleotide in the dominant allele might result in a codon coding for different amino acid.

Despite of one normal allele, the person get disease as the mutated allele suppresses the expression of normal allele, leading to severe consequences. This results into the failure of the production of required transcription factor, due to which developmental malformation happened.

Conclusion

Therefore, it can be concluded that missense mutation in a gene that encodes for a transcription factorresults into developmental malformation, even if one normal allele is present.

Answer 8

Expert Solution & Answer

Summary Introduction

Case summary:

In this case16 of 36 members of a large family were found to have one of the two malformations of the feet called claw foot (CMT) or rocker bottom foot (CVT). Even one individual had both the affected foot, one with CVT and the other with CMT.

Characters in the case:

A family with varying foot malformations.

Adequate information:

HOXD homeotic gene cluster in humans is involved in limb development. A single missense mutationhas been recognized in the HOXD10 gene by genomic analysis. As a result, substitution of a single amino acid took place in the homeodomain of the encoded transcription factor. This region is important as it makes contact and binds to the target genes directed by this protein.

To determine:

A dominant mutation in a gene encoding a transcription factor lead to a developmental malformation.

Given information:

The affected heterozygotes carry one normal allele of the HOXD10 gene, while all unaffected members are homozygous and carry normal alleles.

Explanation of Solution

HOX gene cluster has a role in the development of limb and is responsible to give protein products that act as transcription factors. Four clusters of HOXD gene are present: HOXA, HOXC, HOXB, and HOXD. Thus, combination of 2 to 4 HOX genes form particular structures. Therefore, mutations in only one HOX gene do not result into complete transformation.

HOXD10 belongs to a cluster of HOXD genes located on chromosome 2. Mutations in this gene causes congenital vertical talus (rocker bottom foot or claw foot). A missense mutation was observed in HOXD10 gene, in which substitution of a single nucleotide in the dominant allele might result in a codon coding for different amino acid.

Despite of one normal allele, the person get disease as the mutated allele suppresses the expression of normal allele, leading to severe consequences. This results into the failure of the production of required transcription factor, due to which developmental malformation happened.

Conclusion

Therefore, it can be concluded that missense mutation in a gene that encodes for a transcription factorresults into developmental malformation, even if one normal allele is present.

Answer 9

Expert Solution & Answer

Answer 10

Expert Solution & Answer

Answer 11

Summary Introduction

Case summary:

In this case16 of 36 members of a large family were found to have one of the two malformations of the feet called claw foot (CMT) or rocker bottom foot (CVT). Even one individual had both the affected foot, one with CVT and the other with CMT.

Characters in the case:

A family with varying foot malformations.

Adequate information:

HOXD homeotic gene cluster in humans is involved in limb development. A single missense mutationhas been recognized in the HOXD10 gene by genomic analysis. As a result, substitution of a single amino acid took place in the homeodomain of the encoded transcription factor. This region is important as it makes contact and binds to the target genes directed by this protein.

To determine:

A dominant mutation in a gene encoding a transcription factor lead to a developmental malformation.

Given information:

The affected heterozygotes carry one normal allele of the HOXD10 gene, while all unaffected members are homozygous and carry normal alleles.

Answer 12

Explanation of Solution

HOX gene cluster has a role in the development of limb and is responsible to give protein products that act as transcription factors. Four clusters of HOXD gene are present: HOXA, HOXC, HOXB, and HOXD. Thus, combination of 2 to 4 HOX genes form particular structures. Therefore, mutations in only one HOX gene do not result into complete transformation.

HOXD10 belongs to a cluster of HOXD genes located on chromosome 2. Mutations in this gene causes congenital vertical talus (rocker bottom foot or claw foot). A missense mutation was observed in HOXD10 gene, in which substitution of a single nucleotide in the dominant allele might result in a codon coding for different amino acid.

Despite of one normal allele, the person get disease as the mutated allele suppresses the expression of normal allele, leading to severe consequences. This results into the failure of the production of required transcription factor, due to which developmental malformation happened.

Answer 13

Conclusion

Therefore, it can be concluded that missense mutation in a gene that encodes for a transcription factorresults into developmental malformation, even if one normal allele is present.

Answer 14

Ch. 20 - CASE STUDY |One foot or another In humans the...Ch. 20 - CASE STUDY| One foot or another In humans the HOXD...Ch. 20 - CASE STUDY| One foot or another In humans the HOXD...Ch. 20 - HOW DO WE KNOW? In this chapter, we have focused...Ch. 20 - Review the Chapter Concepts list on page 403. Most...Ch. 20 - 3. Nuclei from almost any source may be injected...Ch. 20 - 4. Distinguish between the syncytial blastoderm...Ch. 20 - (a) What are maternal-effect genes? (b) When are...Ch. 20 - (a) What are zygotic genes, and when are their...Ch. 20 - List the main classes of zygotic genes. What is...

Concept explainers

Videos

Explanation of Solution

Want to see more full solutions like this?

Chapter 20 Solutions