Daisy inherits a mutation from her mother that results in the phenotype of red hair. Evegny acquires a mutation in a cell in his pancreas as a result of exposure to high levels of radiation. What is the difference between these two mutations? Which of these two individuals will pass their mutation to offspring? Because Daisy's and Evegny's mutations are both found in somatic cells, neither Daisy nor Evegny will pass their mutation to their children. Daisy's mutation is in both somatic and germline cells, while Evegny's is only in a small number of somatic cells. Only Daisy will pass on her mutation. Evegny's mutation is in somatic cells, while Daisy's is in somatic and germline cells. Only Evegny will pass the mutation to his children. While these two mutations originate from different sources, both Daisy and Evegny can pass their mutations to their children. O O O

As a physician, you deliver a baby with protruding heels and clenched fists with the second and fifth fingers over-lapping the third and fourth fingers. a. What genetic disorder do you suspect the baby has? b. How do you confirm your suspicion?

Theodor Boveri predicted that malignancies would often be associated with chromosomal mutation. What lines of evidence substantiate this prediction?

One unexpected result of the sequencing of the human genome was the finding that mutations in a single gene can be responsible for multiple distinct disorders. For example, mutations in the RET gene can cause two different types of multiple endocrine neoplasias, familial medullary thyroid carcinoma, and Hirschsprung disease. How do you think mutations in a single gene can have such diverse effects?

The cystic fibrosis gene encodes a chloride channel protein necessary for normal cellular functions. Let us assume that if at least 5% normal channels are present, the affected individual has mild symptoms of cystic fibrosis. Having less than 5% normal channels produces severe symptoms. At least 50% of the channels must be expressed for the individual to be phenotypically normal. This gene has various mutant recessive alleles: Predict the percent of functional channels and severity of symptoms for the following genotypes: a. heterozygous for CF100 b. homozygous for CF100 c. heterozygous, with one copy of CF100 and one of CF3 d. heterozygous, with one copy of CF1 and one copy of CF3

Although it is well known that X-rays cause mutations, they are routinely used to diagnose medical problems, including potential tumors, broken bones, and dental cavities. Why is this done? What precautions need to be taken?

What are the roles of cellular proto-oncogenes, and how are these roles consistent with their implication in oncogenesis?

In Section 12-1, Julie is concerned that she may develop breast cancer, but testing shows that she does not carry the rare high-risk BRCA1 and BRCA2 alleles. What if further testing showed that some of her aunts, her mother, and she carried a common low-risk allele for breast cancer. What would you recommend to Julie if you were her genetic counselor?

Phenylketonuria and alkaptonuria are both autosomal recessive diseases. If a person with PKU marries a person with AKU, what will the phenotype of their children be?

A couple was referred for genetic counseling because they wanted to know the chances of having a child with dwarfism. Both the man and the woman had achondroplasia (MIM 100800), the most common form of short-limbed dwarfism. The couple knew that this condition is inherited as an autosomal dominant trait, but they were unsure what kind of physical manifestations a child would have if it inherited both mutant alleles. They were each heterozygous for the FGFR3 (MIM 134934) allele that causes achondroplasia. Normally, the protein encoded by this gene interacts with growth factors outside the cell and receives signals that control growth and development. In achrodroplasia, a mutation alters the activity of the receptor, resulting in a characteristic form of dwarfism. Because both the normal and mutant forms of the FGFR3 protein act before birth, no treatment for achrondroplasia is available. The parents each carry one normal allele and one mutant allele of FGRF3, and they wanted information on their chances of having a homozygous child. The counsellor briefly reviewed the phenotypic features of individuals with achondroplasia. These include facial features (large head with prominent forehead; small, flat nasal bridge; and prominent jaw), very short stature, and shortening of the arms and legs. Physical examination and skeletal X-ray films are used to diagnose this condition. Final adult height is approximately 4 feet. Because achondroplasia is an autosomal dominant condition, a heterozygote has a 1-in-2, or 50%, chance of passing this trait to his or her offspring. However, about 75% of those with achondroplasia have parents of average size who do not carry the mutant allele. In these cases, achondroplasia is due to a new mutation. In the couple being counseled, each individual is heterozygous, and they are at risk for having a homozygous child with two copies of the mutated gene. Infants with homozygous achondroplasia are either stillborn or die shortly after birth. The counselor recommended prenatal diagnosis via ultrasounds at various stages of development. In addition, a DNA test is available to detect the homozygous condition prenatally. What is the chance that this couple will have a child with two copies of the dominant mutant gene? What is the chance that the child will have normal height?