Question

The following table shows neutral polymorphisms found in control families (those with no increased frequency of breast and ovarian cancer). Examine the data in the table and answer the following questions: (a) What is meant by a neutral polymorphism? (b) What is the significance of this table in the context of examining a family or population for \(B R C A 1\) mutations that predispose an individual to cancer? (c) Is the PM2 polymorphism likely to result in a neutral missense mutation or a silent mutation? (d) Answer part (c) for the PM3 polymorphism.

Short answer

Answer: A neutral polymorphism is a genetic variation within a population that does not have any significant effect on the phenotype or the fitness of the individuals. It is useful for examining BRCA1 mutations in a population because it helps to identify which polymorphisms can be ruled out as potential factors predisposing an individual to breast and ovarian cancer. Since the neutral polymorphisms are unlikely to contribute to an increased risk of cancer, researchers can focus on other genetic variations that may be responsible for predisposing an individual to cancer.

Step-by-step solution

a) Neutral Polymorphism Definition

A neutral polymorphism is a genetic variation within a population that does not have any significant effect on the phenotype or the fitness of the individuals. It means that the change in the DNA sequence does not lead to any harmful or beneficial consequences and remains relatively stable in the population.

b) Significance of the Table for Examining BRCA1 Mutations

The significance of the table in the context of examining a family or population for BRCA1 mutations is that it helps to identify which polymorphisms can be ruled out as potential factors predisposing an individual to breast and ovarian cancer. Since the table shows neutral polymorphisms, it is likely that these genetic variations do not contribute to an increased risk of cancer. By knowing which polymorphisms are neutral, researchers can focus on other genetic variations that may be responsible for predisposing an individual to cancer.

c) PM2 Polymorphism Mutation Type

To determine if the PM2 polymorphism is likely to result in a neutral missense mutation or a silent mutation, we need to examine the change in the DNA sequence and its consequence on the amino acid sequence of the protein. If the change in the nucleotide sequence leads to a substitution of one amino acid with another, but the new amino acid does not affect the protein function, the mutation is a neutral missense mutation. On the other hand, if the change in the nucleotide sequence does not affect the amino acid sequence, the mutation is considered a silent mutation.

d) PM3 Polymorphism Mutation Type

Similar to question (c), we need to examine the change in the DNA sequence and its consequence on the amino acid sequence of the protein for the PM3 polymorphism. If the PM3 polymorphism leads to a substitution of one amino acid with another without affecting the protein function, it is a neutral missense mutation. If there is no change in the amino acid sequence due to the PM3 polymorphism, it is considered a silent mutation.

Key concepts

BRCA1 Mutations

Understanding BRCA1 mutations is key to unraveling the complex relationship between genetics and cancer risk. The BRCA1 gene, which stands for Breast Cancer 1, is responsible for DNA repair, and when functioning properly, it helps to suppress tumors. Mutations in BRCA1 can impair this function and lead to an increased risk of breast and ovarian cancer.

Not all mutations have the same impact. Some can be deleterious, while others, known as neutral polymorphisms, have no significant effect on an individual’s health. These neutral polymorphisms can occur frequently within populations and can be used as a genetic baseline to distinguish between harmful BRCA1 mutations and benign variations.

Genetic Variation

The concept of genetic variation is fundamental to the study of biology and medicine. It is the diversity in DNA sequences among individuals within a species.

Genetic variations can manifest as single nucleotide polymorphisms (SNPs), insertions, deletions, or even larger structural changes. This variation is important because it contributes to an individual's unique traits and can influence susceptibility to diseases or response to medications. In the context of BRCA1 mutations, understanding the landscape of genetic variation is crucial for identifying which changes are potentially harmful and which are not.

Missense Mutation

A missense mutation is a type of genetic mutation where a single nucleotide change results in the substitution of a different amino acid in the protein sequence.

Exploring Missense Mutations:

• If the new amino acid does not significantly alter the protein's structure or function, it's considered a neutral missense mutation.
• However, if the alteration impairs protein function, it can be pathogenic and possibly linked to diseases like cancer.

Exercise Improvement: In the context of the PM2 polymorphism, deciding whether it's a neutral missense mutation involves analyzing whether the resultant amino acid change affects the BRCA1 protein's function.

Silent Mutation

A silent mutation is a specific type of mutation where a change in the DNA sequence does not alter the amino acid sequence of the resulting protein. This is often due to the redundancy in the genetic code—multiple codons can encode for the same amino acid.

Characteristics of Silent Mutations:

• These mutations are typically considered neutral.
• They do not affect the phenotype and are often undetectable without genetic testing.

Silent mutations in BRCA1, such as a potential PM3 polymorphism, would not change the function of the protein and hence would not contribute to cancer risk, which aligns with the concept of neutral polymorphism.