Context

World Down Syndrome Day, WDSD is observed every year on 21st March. It is a global campaign that is observed annually to spread awareness about Down Syndrome.

Background

• WDSD is officially observed by the United Nations since 2012.
• March 21 was selected to signify the uniqueness of the triplication of the 21st chromosome which causes Down syndrome, a disorder that affects approximately 6,000 babies at birth every year.
• It is usually associated with physical growth delays, mild to moderate intellectual disability, and characteristic facial features.

Analysis

What are chromosomal aberrations?

• Chromosomal aberrations, or abnormalities, are changes to the structure or number of chromosomes, which are strands of condensed genetic material.
• Humans typically have 23 pairs of chromosomes, of which 22 pairs are autosomal, numbered 1 through 22.
• The last pair of chromosomes are sex chromosomes, which determine an individual’s sex assignment.
• At birth, most people with XY sex chromosomes are assigned male, and most individuals with XX are assigned female.
• In general, each parent contributes one set of chromosomes to their offspring, which collectively make up the 23 pairs of chromosomes.
• A change to any of the chromosomes, in number or structure, creates a chromosomal aberration and may cause medical disorders.

Chromosomal disorders due to numerical abnormalities:

• Chromosomal disorders are due to the change in the number of chromosomes present. This can be categorized into various types:
• Aneuploidy: loss or gain of a chromosome. This happens due to non-disjunction of chromatids when chromatids fail to separate during cell division. This results in one gamete having two copies of one chromosome and the other having no chromosome.
  • Trisomy: The cell has one extra chromosome (2n+1)
  • Monosomy: The cell has one chromosome less (2n-1)
  • Aneuploidy can be due to nondisjunction of autosomes i.e. chromosomes 1-22 or sex chromosomes.
• Euploidy: Loss or gain of the whole set of chromosome. Mostly occurs in plants.
  • Haploid: Loss of one set of the chromosomes, i.e. ‘n’ number of chromosomes
  • Polyploid: Addition of one or more set of chromosomes, e.g. ‘3n (triploid)’, ‘6n (hexaploid)’ etc.
• Examples of numerical abnormalities:
  • Down’s Syndrome: Trisomy of 21^st chromosome
  • Patau’s Syndrome: Trisomy of 13^th chromosome
  • Edward’s Syndrome: Trisomy of 18^th chromosome
  • Klinefelter’s Syndrome: Trisomy of sex chromosome (XXY)
  • Super Female Syndrome: Trisomy of Sex chromosome (XXX)
  • Turner’s Syndrome: Monosomy of sex chromosome (X0)

Chromosomal disorders due to structural abnormalities:

This happens when a large set of genes are deleted, duplicated or rearranged causing structural changes in the chromosome. Structural abnormalities can be due to:

Deletion: A portion of the chromosome is lost during cell division.

Example of disorder due to deletion:

• • Cri du chat (cry of the cat): Deletion of a small portion of 5th chromosome. Children with this disease have a small head with unusual facial features, severe mental retardation and make a sound like a cat while crying.

Duplication: The presence of part of a chromosome in excess is known as duplication.

• Tandem duplication, where the duplicated region is present side by side (ABCDEF→ABCDEDEF)
• Reverse tandem, here duplicated region is just reverse of the normal sequence (ABCDEF→ABCDEEDF)
• Displaced duplication, here duplicated region is not situated adjacent to the normal sequence
• Example of disorder due to duplication:
  • Fragile X: Affects 1:1500 males and 1:2500 females. This is the most common form of mental retardation, where the CGS segment is repeated more than 200 times.

Inversion: inversion results from breakage and reunion of a part of the chromosome rotating by 180° on its own axis. So there occurs a rearrangement of genes. Its effects are not as severe as in other structural defects

Translocation: The shifting or transfer of a set of genes or part of a chromosome to a non-homologous one is known as translocation. There is no addition or loss of genes, only the rearrangement occurs. This rearrangement may lead to phenotype changes pertaining to the new environment. It can cause difficulties in the development of egg, sperm or zygote. These often result in miscarriages and children born with disabilities.

• Example of disorder due to translocation:
  • Acute Myelogenous Leukemia: In this type of cancer, bone marrow and cells derived from it show the presence of a short chromosome named as “Philadelphia (Ph1) chromosome”. The 22nd chromosome loses a part of its arm which gets translocated to the distal end of the 9th chromosome. It is not transmitted to the offspring.

How can one reduce the risk of chromosomal aberrations?

• Parents may reduce some risk of chromosomal aberrations in offspring by meeting their own nutritional needs, limiting exposure to problematic substances, and visiting a doctor before becoming pregnant.
• General risk reduction strategies include eating healthy, abstaining from smoking or drinking alcohol, and taking prenatal vitamins prior to pregnancy.
• Chromosomal aberrations are more likely to occur in pregnancies when the pregnant individual is over the age of 35.
• If a chromosomal disorder has been identified in a family, a healthcare provider may recommend genetic counseling to discuss different options, including assisted reproduction techniques.