Question

In this chapter, we have focused on chromosomal mutations resulting from a change in number or arrangement of chromosomes. In our discussions, we found many opportunities to consider the methods and reasoning by which much of this information was acquired. From the explanations given in the chapter, what answers would you propose to the following fundamental questions? (a) How do we know that the extra chromosome causing Down syndrome is usually maternal in origin? (b) How do we know that human ancuploidy for each of the 22 autosomes occurs at conception, even though most often human aneuploids do not survive embryonic or fetal development and thus are never observed at birth? (c) How do we know that specific mutant phenotypes are due to changes in chromosome number or structure? (d) How do we know that the mutant Bar-eye phenotype in Drosophila is due to a duplicated gene region rather than to a change in the nucleotide sequence of a gene?

Short answer

Answer: The most common origin of the extra chromosome in Down syndrome cases is maternal, which accounts for around 90-95% of cases. This is determined through DNA polymorphism analysis or molecular genetic techniques that allow researchers to identify whether the extra chromosome originated from the mother or the father.

Step-by-step solution

(a) Extra chromosome in Down syndrome

To answer this question, we need to discuss how researchers have found that the extra chromosome causing Down syndrome is usually maternal in origin. Step 1: Observe the patients with Down syndrome Researchers observed that individuals with Down syndrome have 47 chromosomes instead of the usual 46. The extra chromosome is a third copy of chromosome 21, also known as trisomy 21. Step 2: Examine the maternal and paternal origins of trisomy 21 Researchers study the origin of the extra chromosome in the affected individuals, typically using DNA polymorphism analysis or molecular genetic techniques. This allows them to determine whether the extra chromosome originated from the mother or the father. Step 3: Analyze the results The results of these studies show that in around 90-95% of cases, the extra chromosome in individuals with Down syndrome is maternal in origin. This suggests that the extra chromosome typically comes from the mother.

(b) Human aneuploidy at conception

To explain how we know that human aneuploidy occurs at conception even though most affected individuals do not survive embryonic or fetal development, we need to discuss how scientists reach this conclusion. Step 1: Study the frequency of aneuploidy in early embryos Researchers have investigated the frequency of chromosomal abnormalities in human embryos, often by examining preimplantation embryos or analyzing products of conception. Step 2: Compare the frequency of aneuploidy at conception and birth The frequency of aneuploidy in early embryos is much higher than the frequency observed in live births, suggesting that many affected embryos do not survive to birth. Step 3: Understand the natural selection process The high rate of aneuploidy at conception, as compared to relatively low rates at birth, shows that natural selection occurs before birth, largely driving the reduction in observable chromosomal abnormalities in live births. This implies that human aneuploidy does occur at conception, even if it is often not observed at birth.

(c) Mutant phenotypes and changes in chromosome number or structure

To explain how we know that specific mutant phenotypes are due to changes in chromosome number or structure, we must discuss the methods researchers use to link these chromosomal changes to phenotypes. Step 1: Observe mutant phenotypes Researchers first identify organisms with an unusual or mutant phenotype. Step 2: Analyze the chromosomes in these organisms By using techniques such as karyotyping or molecular genetic analyses, researchers can identify structural or numerical chromosome differences in affected organisms. Step 3: Establish a correlation between the mutant phenotype and chromosome changes If the same chromosome abnormalities are consistently found in organisms with identical mutant phenotypes, then a strong correlation between the phenotype and the chromosomal change is established.

(d) Bar-eye phenotype in Drosophila

To demonstrate that the mutant Bar-eye phenotype in Drosophila is due to a duplicated gene region rather than to a change in the nucleotide sequence of a gene, we need to go through the steps of analyzing this phenomenon. Step 1: Observe the Bar-eye phenotype in Drosophila Researchers identified the Bar-eye phenotype in Drosophila, characterized by a reduced and narrow eye shape. Step 2: Analyze the genetic basis of the Bar-eye phenotype Using genetic analyses, researchers found that this phenotype was not due to a single nucleotide change, but instead was associated with changes in gene dosage. Step 3: Identify the duplicated gene region Further research revealed that the Bar-eye phenotype is caused by a tandem duplication of a region of the X chromosome. This duplication causes an increased dosage of the genes within that region, which in turn leads to the observed phenotype. In summary, by investigating each fundamental question regarding chromosomal mutations, we were able to address the specific aspects of chromosome abnormalities and their causes in Down syndrome, human aneuploidy, mutant phenotypes, and the Bar-eye phenotype in Drosophila.

Key concepts

Aneuploidy

Aneuploidy is a type of chromosomal mutation that involves an abnormal number of chromosomes. This condition occurs when organisms have either fewer or additional chromosomes compared to the normal set. Typically, humans have 46 chromosomes, which includes 22 pairs of autosomes and one pair of sex chromosomes. Aneuploidy results when there is a deviation from this number of chromosomes.

Causes of aneuploidy can include errors during cell division, particularly during meiosis, when the chromosomes do not separate properly. This error is known as nondisjunction.

• If nondisjunction happens during meiosis I, homologous chromosomes may fail to separate.
• If it occurs during meiosis II, sister chromatids may not separate correctly.

These errors lead to gametes with an incorrect number of chromosomes, and when they fertilize, the result is an organism with an abnormal chromosome number.

Most aneuploid conditions are not compatible with life, leading to miscarriages, but some, like Down syndrome, do result in a viable pregnancy. This is why many instances of aneuploidy are only detectable in early-stage embryos or through genetic analysis.

Trisomy 21

Trisomy 21, commonly known as Down syndrome, occurs when an individual has three copies of chromosome 21 instead of the usual two. It is one of the few aneuploidies that allow for survival past birth, although it results in a range of developmental and intellectual disabilities.

Trisomy 21 has been extensively studied, and it is well-documented that in 90-95% of the cases, the extra chromosome is maternal in origin. This is often due to nondisjunction during the mother's meiosis. To determine the parental origin of the extra chromosome, scientists use techniques such as DNA polymorphism analysis. By examining markers on the DNA, they can pinpoint which parent contributed the additional chromosome.

Individuals with Down syndrome exhibit characteristic physical attributes and may have varying degrees of cognitive impairment. However, they also face an increased risk for certain medical conditions such as heart defects and respiratory issues. Despite these challenges, many people with Down syndrome lead fulfilling lives with the support of medical and educational interventions.

Gene Duplication

Gene duplication is a chromosomal mutation where a segment of the chromosome is copied, resulting in multiple copies of a particular gene or region on the chromosome. This can have significant implications for the organism, as having extra copies of a gene can alter the gene's expression and lead to phenotypic changes.

An excellent example of gene duplication's effect is observed in the Bar-eye phenotype in Drosophila. These flies have a distinctive eye shape due to increased gene dosage, which is the result of a tandem duplication of a region on the X chromosome. Instead of a mutation in the sequence of a single gene, the presence of additional gene copies leads to the phenotype.

• Gene duplication can occur through errors in DNA replication or unequal crossing over during meiosis.
• Though often detrimental, gene duplications can occasionally confer advantages and play a role in evolution by providing raw material for new gene functions.

Overall, gene duplications highlight the importance of gene dosage and how changes in gene number can impact organism development and characteristics.