THE SCIENCE OF CHROMOSOMES

Introduction

Chromosomes are long, coiled-up molecules of DNA (deoxyribonucleic acid) that contain an organism’s genetic information. They are found in the nucleus of every cell in the body of eukaryotic organisms, including humans. Chromosomes are responsible for transmitting genetic information from one generation to the next during the process of cell division.

Each chromosome is made up of two identical chromatids that are held together by a structure called the centromere. Chromosomes are numbered according to their size, with the largest chromosome being chromosome 1 and the smallest being chromosome 22 (in humans). Additionally, there are two sex chromosomes, X and Y, that determine an individual’s sex.

The number of chromosomes varies between different species. For example, humans have 46 chromosomes (23 pairs), while dogs have 78 chromosomes (39 pairs) and fruit flies have only 8 chromosomes (4 pairs). Chromosomal abnormalities, such as having an extra or missing chromosome, can lead to genetic disorders and diseases.

 

Chromosomes are structures made up of DNA and proteins found in the nucleus of cells. They carry genetic information in the form of genes, which are segments of DNA that encode specific traits or characteristics.

The typical chromosome structure can be divided into four main parts:

1. Centromere: This is the region of the chromosome that holds the two sister chromatids together.
2. Telomeres: These are the ends of the chromosome that protect it from damage and prevent it from sticking to other chromosomes.
3. Arms: These are the two sections of the chromosome on either side of the centromere.
4. Chromatids: These are the two identical copies of DNA that make up a chromosome after it has replicated.

In humans, the normal chromosome complement is 46 chromosomes. This means that each cell in the human body (with a few exceptions) contains 23 pairs of chromosomes. One chromosome in each pair comes from the mother and the other from the father. Of these 46 chromosomes, 44 are autosomes (non-sex chromosomes) and two are sex chromosomes, which determine the biological sex of an individual. Females have two X chromosomes (46,XX) and males have one X and one Y chromosome (46,XY).

 

Sex determination is the process by which an individual’s sex is established, and it can vary depending on the organism. In humans, sex is determined by the presence of sex chromosomes in the individual’s cells. Most females have two X chromosomes (XX), while most males have one X and one Y chromosome (XY).

Abnormalities in the sex chromosomes can occur due to errors during meiosis, the process by which sex cells are produced. Some common examples of sex chromosome abnormalities in humans include:

1. Turner Syndrome: This occurs when a female is born with only one X chromosome (45,X). Turner syndrome is characterized by short stature, infertility, and other physical abnormalities.
2. Klinefelter Syndrome: This occurs when a male is born with an extra X chromosome (47,XXY). Klinefelter syndrome is characterized by reduced testosterone levels, infertility, and other physical and cognitive abnormalities.
3. Triple X Syndrome: This occurs when a female is born with an extra X chromosome (47,XXX). Triple X syndrome is often asymptomatic but can be associated with learning disabilities and other developmental issues.
4. XYY Syndrome: This occurs when a male is born with an extra Y chromosome (47,XYY). XYY syndrome is often asymptomatic but can be associated with increased height and behavioral issues.
5. Androgen insensitivity syndrome: This occurs when a person with XY chromosomes is unable to respond to androgens (male sex hormones) due to a genetic mutation. Individuals with androgen insensitivity syndrome may have female physical characteristics but have testes instead of ovaries.

These are just a few examples of the many possible sex chromosome abnormalities. Many of these conditions are rare and may not be diagnosed until later in life or may go undiagnosed altogether.

 

Array comparative genomic hybridization (array CGH) is a powerful tool for analyzing the chromosome complement of a cell or organism. This technique is widely used in genetic research and clinical applications to detect chromosomal abnormalities such as deletions, duplications, and copy number variations (CNVs).

Array CGH works by comparing the DNA of a test sample (e.g. patient’s DNA) with a reference sample (e.g. normal DNA) using a microarray chip containing thousands or millions of DNA probes. The probes on the chip are designed to detect specific regions of the genome, and the intensity of the signals from the test and reference samples at each probe location is compared. Any differences in signal intensity between the test and reference samples indicate chromosomal abnormalities.

Array CGH has several advantages over traditional cytogenetic methods such as karyotyping, which relies on the visual analysis of chromosomes under a microscope. First, array CGH can detect much smaller chromosomal abnormalities than karyotyping, as it can detect CNVs as small as a few kilobases in size. Second, array CGH is much faster and can analyze many more samples at once than karyotyping. Third, array CGH is more objective and less prone to human error than karyotyping.

Array CGH has become the standard tool for analyzing the chromosome complement in many research and clinical settings. It has been used to identify chromosomal abnormalities in a wide range of conditions, including developmental disorders, intellectual disability, autism, cancer, and infertility. The results of array CGH can guide clinical management, such as providing a diagnosis, informing genetic counseling, and identifying potential treatment options.

In conclusion, array CGH is a powerful and widely used tool for analyzing the chromosome complement of a cell or organism. It provides a more sensitive, faster, and objective method for detecting chromosomal abnormalities compared to traditional cytogenetic methods. As such, it has become the standard tool in many research and clinical settings for diagnosing and managing a wide range of genetic conditions.

 

Chromosomal abnormalities refer to any changes or errors that occur in the structure or number of chromosomes in an organism’s cells. These abnormalities can have significant effects on an individual’s development, growth, and overall health. Here are some examples of chromosomal abnormalities and their effects:

1. Down syndrome: Down syndrome is one of the most common chromosomal abnormalities, occurring in approximately 1 in 700 births. It results from the presence of an extra copy of chromosome 21, which can lead to developmental delays, intellectual disability, and certain physical features such as a small head, short stature, and a flattened face.
2. Turner syndrome: Turner syndrome occurs when one of the X chromosomes is missing or incomplete, affecting only females. It can cause short stature, delayed puberty, infertility, heart and kidney abnormalities, and learning difficulties.
3. Klinefelter syndrome: Klinefelter syndrome is caused by the presence of an extra X chromosome in males, resulting in smaller testicles, reduced fertility, and increased risk of breast cancer.
4. Cri du chat syndrome: Cri du chat syndrome results from a deletion in the short arm of chromosome 5, leading to intellectual disability, delayed development, and distinct facial features.
5. Patau syndrome: Patau syndrome, also known as trisomy 13, is caused by the presence of an extra copy of chromosome 13. It can cause severe intellectual disability, congenital heart defects, and other physical abnormalities.
6. Edwards syndrome: Edwards syndrome, or trisomy 18, occurs when there is an extra copy of chromosome 18. It can lead to severe intellectual disability, heart and kidney defects, and other physical abnormalities.

These are just a few examples of the many chromosomal abnormalities that can occur. They can have a wide range of effects, from mild to severe, and can impact many aspects of an individual’s life.

 

1) Down Syndrome

Clinical features: Intellectual disability, characteristic facial features, short stature, hypotonia, congenital heart defects, gastrointestinal anomalies, hearing loss, and increased risk of leukemia.

Karyotype: Trisomy 21 (47,XX,+21 or 47,XY,+21)

 

2) Patau Syndrome

Clinical features: Intellectual disability, microcephaly, characteristic facial features, cleft lip/palate, polydactyly, rocker-bottom feet, congenital heart defects, and severe organ abnormalities.

Karyotype: Trisomy 13 (47,XX,+13 or 47,XY,+13)

 

3) Edwards Syndrome

Clinical features: Intellectual disability, microcephaly, characteristic facial features, clenched fists with overlapping fingers, rocker-bottom feet, congenital heart defects, and severe organ abnormalities.

Karyotype: Trisomy 18 (47,XX,+18 or 47,XY,+18)

 

4) Turner Syndrome: Clinical features: Short stature, webbed neck, broad chest, underdeveloped ovaries, amenorrhea, infertility, heart and kidney abnormalities, and hearing loss.

Karyotype: Monosomy X (45,X)

 

5) Klinefelter Syndrome

Clinical features: Tall stature, small testes, infertility, gynecomastia, reduced body hair, and increased risk of breast cancer and osteoporosis.

Karyotype: Trisomy XXY (47,XXY)

 

 

Numerical abnormalities

Aneuploidy: An abnormal number of chromosomes, which can be either monosomy (missing a chromosome) or trisomy (having an extra chromosome).

 

Structural abnormalities

Balanced translocations: A type of chromosomal rearrangement in which two chromosomes exchange segments without any gain or loss of genetic material.

Unbalanced translocations: A type of chromosomal rearrangement in which there is an unequal exchange of genetic material between two chromosomes, resulting in loss or gain of genetic material.

Robertsonian translocations: A type of chromosomal rearrangement in which the long arms of two acrocentric chromosomes fuse, resulting in a single large chromosome.

Duplications: A type of chromosomal abnormality in which a segment of chromosome is duplicated.

Deletions: A type of chromosomal abnormality in which a segment of chromosome is missing.

Inversions: A type of chromosomal rearrangement in which a segment of chromosome is flipped in orientation.