biol 117 quiz 5

Why is aneuploidy more common in oocytes than in sperm?

Sperm have meiotic checkpoints that can stop cells with problems, while oocytes lack some of these checkpoints. 

Why is aneuploidy more common in female humans than in female mice?

 Human oocytes must maintain chromosome connections for much longer, possibly decades, which may cause more problems over time. 

How does maternal age relate to the likelihood of aneuploidy?

The risk of aneuploidy increases as maternal age increases. 

 How do the mechanisms that give rise to aneuploidy often differ between young and older women?

In older women, problems with chromosome cohesion and recombination become more common, which can cause chromosomes to separate incorrectly.

How does the timing of meiosis I in females likely contribute to increased aneuploidy with age?

Meiosis I begins before birth and then pauses for years or decades before continuing. This long period may cause the chromosome connections and other structures to deteriorate.

What role does cohesion play in recombination and aneuploidy?

Cohesin holds sister chromatids together and helps maintain stable chromosome connections. Losing cohesion can cause improper chromosome separation and aneuploidy. 

How does the observation that dominant, X-linked mutations almost exclusively affect girls suggest a higher mutation rate in the male germline? Would we expect only girls to be affected if mutation rates were the same?

The mutations are almost exclusively paternal in origin, showing that new mutations occur more often in the male germline. If mutation rates were equal, we would not expect the mutations to almost exclusively affect girls.

 How do we know that all mutations in X-linked dominant reproductive lethal genes are sporadic?

There are almost no affected males who could reproduce and pass the mutations on, and DNA sequencing shows that the mutations are almost entirely paternal in origin. 

What type of new mutations usually arise in the paternal germline, and how does this suggest mismatch repair defects?

Base substitutions are especially common in the paternal germline. Since mismatch repair fixes single-base changes and small replication loops, less efficient mismatch repair in the male germline could explain the higher mutation rate. 

What factors may cause the paternal age effect?

Older men have more sperm-cell divisions and DNA replications, giving more opportunities for mutations to occur. Some mutations, especially FGF-R mutations, may also increase because mutant sperm cells gain a growth advantage.

Can the increase in FGF-R mutations be explained by increased mitoses/DNA replication alone? If not, what might explain it?

No. FGF-R mutations occur at rates over 1,000 times higher than normal, so extra replications alone cannot explain them. The mutations give spermatogonial cells a growth advantage, causing clonal expansion and more mutant sperm.

Are most traits determined by single genes or multiple genes?

Most traits are determined by multiple genes and are also influenced by the environment.

What are the hallmarks of multifactorial inheritance?

The trait runs in families but does not follow a simple inheritance pattern. Risk is higher in closer relatives, and having more affected family members increases the recurrence risk.