Sex Chromosomes and Chromosomal Aberrations – Study Notes

Study Guide - Smart Notes

Tailored notes based on your materials, expanded with key definitions, examples, and context.

Sex Determination and Chromosomal Aberrations

Introduction to Reproductive Modes

Organisms exhibit a wide range of reproductive strategies and life cycles. These strategies influence genetic diversity and evolutionary adaptation.

Asexual reproduction: Some organisms reproduce solely by asexual means, producing genetically identical offspring.
Sexual reproduction: Others reproduce sexually, involving the fusion of gametes from two parents, increasing genetic variation.
Mixed strategies: Many species alternate between sexual and asexual reproduction, often with sexual reproduction occurring during short periods and asexual reproduction dominating longer periods.
Sexual differentiation: In complex organisms, sexual reproduction requires differentiation into male and female forms, often visible as phenotypic dimorphism.

Sex Chromosomes and Their Role

Sex chromosomes are specialized chromosomes that determine the sex of an organism. In mammals, these are the X and Y chromosomes.

Heteromorphic chromosomes: The XY system in mammals is an example, where males are typically XY and females XX.
Sex chromosomes: The X and Y chromosomes are called sex chromosomes, while the other 22 pairs are autosomes.
Chromosome naming: The X chromosome was named for its unique properties, and the Y chromosome was named sequentially.

Human Sex Chromosomes

Y Chromosome:
- Present only in males.
- Contains approximately 55 genes, most of which are Y-specific.
- Small regions at the ends, called pseudoautosomal regions (PARs), share homology with the X chromosome and allow for pairing during meiosis.
X Chromosome:
- Present in both males and females.
- Contains about 900 genes, much more than the Y chromosome.
- Genes on the X chromosome function in both sexes.

SRY Gene and Sex Determination

The SRY (Sex-determining Region Y) gene is the primary genetic signal for male development in mammals.

Presence of Y chromosome: Individuals with a Y chromosome are typically male, regardless of the number of X chromosomes.
SRY gene: Encodes the testis-determining factor (TDF), which initiates male sex determination.
SRY present: Embryonic gonadal cells develop into testes, which produce testosterone and anti-Müllerian hormone (AMH), leading to male differentiation.
SRY absent: Embryonic gonadal cells develop into ovaries, and female characteristics develop.
Transgenic studies: XX mice with an SRY transgene develop as males, demonstrating the gene's pivotal role.

Environmental Sex Determination

In some species, environmental factors such as temperature determine sex, a phenomenon known as Temperature-Dependent Sex Determination (TSD).

Common in reptiles, including all crocodiles, most turtles, and some lizards.
Temperature influences the activity of enzymes that control steroid sex hormone levels, affecting the transcription of key genes involved in sex determination.

Chromosomal Aberrations

Types of Chromosomal Aberrations

Chromosomal aberrations are structural or numerical changes in chromosomes that can have significant genetic consequences.

Aneuploidy: Change in chromosome number that does not involve complete sets of chromosomes.
- Monosomy: Loss of a single chromosome (2n-1).
- Trisomy: Gain of a single chromosome (2n+1).
Polyploidy: Presence of more than two complete sets of chromosomes (e.g., triploidy = 3n).
Deletions and duplications: Loss or gain of chromosome segments, altering gene dosage.
Inversions: A chromosome segment is reversed end to end, with no loss of genetic material.
Translocations: Exchange or transfer of chromosome segments between nonhomologous chromosomes.

Aneuploidy and Nondisjunction

Aneuploidy often results from nondisjunction, an error during meiosis where chromosomes fail to separate properly.

Nondisjunction: Can occur during meiosis I or II, leading to gametes with abnormal chromosome numbers.
Example conditions: Down syndrome (trisomy 21), Turner syndrome (monosomy X), Klinefelter syndrome (XXY).
Most aneuploidies involving autosomes are lethal, except for a few (e.g., trisomy 21).

Monosomies

Monosomy for the X chromosome (Turner syndrome) occurs in humans.
Monosomy for autosomes is usually lethal in humans and other animals.
Haploinsufficiency: A single copy of a recessive gene is insufficient to provide normal function, leading to phenotypic effects.

Trisomy: Down Syndrome

Trisomy 21 (Down syndrome): Presence of an extra chromosome 21.
Incidence: 1 in 800 live births (4,000–5,000 births annually in the U.S.).
Features: Distinct facial characteristics, cognitive disabilities, increased risk of heart and respiratory issues, decreased risk of solid tumors, average lifespan ~50 years.

Down Syndrome Critical Region (DSCR)

A specific region on chromosome 21 contains dosage-sensitive genes responsible for many Down syndrome phenotypes.
Extra copies of genes in this region, such as DSCR1, are associated with altered cancer risk.
DSCR1 gene: Encodes a protein that inhibits vascular endothelial growth factor (VEGF) signaling, affecting angiogenesis.

Maternal Age and Down Syndrome Incidence

The risk of having a child with Down syndrome increases with maternal age, especially over 40 years.
In 95% of cases, the extra chromosome 21 originates from the ovum.
Diagnostic tests are available for older pregnant women.

Diagnostic Testing for Chromosomal Aberrations

Amniocentesis and chorionic villus sampling (CVS): Invasive procedures to obtain fetal cells for cytogenetic analysis.
Noninvasive prenatal genetic diagnosis (NIPGD): Uses cell-free fetal DNA from maternal blood for genetic testing.

Human Development and Chromosome Number

Karyotype analysis of spontaneously aborted fetuses reveals that a significant proportion of conceptions terminate due to chromosomal imbalances.
Normal embryonic development requires a precise diploid chromosome complement to maintain gene expression equilibrium.

Composition and Arrangement of Chromosomes

Deletions: Loss of chromosome segments, which can be terminal or intercalary.
Duplications: Repetition of chromosome segments, often resulting from unequal crossing over during meiosis.
Inversions: Chromosome segments are reversed; can be pericentric (including centromere) or paracentric (excluding centromere).
Translocations: Exchange of segments between nonhomologous chromosomes; can be reciprocal or nonreciprocal.
These rearrangements can cause phenotypic variation and contribute to evolution.

Causes of Chromosomal Aberrations

Chromosomal aberrations often result from breaks along the chromosomal axis, followed by loss or rearrangement of genetic material.
Breakages can occur spontaneously or be induced by environmental factors such as radiation or chemicals.
Alterations in germ line cells are heritable if they occur during meiosis.

Summary Table: Types of Chromosomal Aberrations

Type	Description	Example
Aneuploidy	Abnormal number of chromosomes (not a multiple of n)	Trisomy 21 (Down syndrome)
Polyploidy	More than two complete sets of chromosomes	Triploidy (3n)
Deletion	Loss of a chromosome segment	Cri-du-chat syndrome (5p deletion)
Duplication	Repetition of a chromosome segment	Charcot-Marie-Tooth disease (17p duplication)
Inversion	Reversal of a chromosome segment	Pericentric inversion of chromosome 9
Translocation	Exchange of segments between nonhomologous chromosomes	Philadelphia chromosome (t(9;22) in CML)

Key Equations

Monosomy:
Trisomy:
Triploidy:

Additional info: These notes expand on the provided lecture slides by filling in missing context, definitions, and examples, ensuring a comprehensive and self-contained study guide for Genetics students.