Overview

Chromosome abnormalities describe abnormalities in the number or structure of a chromosome which can lead to genetic disorders. Broadly speaking, they can be divided into:

  • Numerical abnormalities – the number of chromosomes is abnormal
  • Structural abnormalities – the structure of the chromosome itself is abnormal

Definitions in Genetics

Genes, chromosomes, and alleles

Gene – a sequence of DNA bases that result in the production of a polypeptide

  • An analogy for this would be a recipe for a cake, the recipe is the sequence of DNA, and the cake is the polypeptide

Allele – variants of the same gene that arise due to mutations

  • An analogy for this would be different types of cake. The recipe (gene) still makes a cake (polypeptide), however, it is a different kind of cake

Chromosomes – long molecules of DNA that contain large numbers of genes.

  • An analogy for this would be a book full of recipes for cakes (chromosome). Each recipe (gene) makes a different kind of cake (allele).
  • Chromosomes are visible under light microscopes only after DNA replication has happened (which takes place in the S phase). This gives chromosomes an X-shaped structure consisting of:
    • Two sister chromatids – two copies of a chromosome
    • Centromere – a structure that links the two sister chromatids together
  • Chromosomes have long and short arms:
    • Short arm (p-arm) – p for petite
    • Long arm (q-arm) – because q is next to p in the alphabet

Locus – a fixed region on a chromosome where a particular gene is found.

Autosome – any chromosome that is not a sex chromosome

Sex chromosomes – chromosomes that differ from autosomes in form and size:

  • In humans, the female sex chromosome is X, and the male sex chromosome is Y
  • The Y chromosome is shorter than the X chromosome. This is important in X-linked disorders

Genotype, phenotype, inheritance and linkage

Genotype – the genetic constitution of an organism (the alleles an organism has)

Phenotype – the expression of the genetic constitution and its interactions with the environment

Dominant – an allele that is expressed in the phenotype even if there is one copy

Recessive – an allele that requires two copies to be expressed

Codominant – neither allele is dominant and both are expressed

Autosomal linkage – the tendency of genes that are close together on a chromosome to be inherited together

Sex linkage – genes that are located on the sex chromosomes and appear differently depending on sex:

  • X-linked recessive alleles can be expressed in males as their genotype is XY. This is because the Y chromosome is shorter and there may not be a corresponding dominant allele that would have been expressed instead of the recessive allele.

Karyotype – the complete set of chromosomes in an organism including sizes, shapes, and numbers

Ploidy – the number of copies of complete sets of chromosomes in a cell. Humans have two copies and are diploid.

Numerical Chromosomal Abnormalities

Overview

Aneuploidy describes an abnormal number of chromosomes. This can be:

  • Monosomy – a chromosome is missing from a pair and only one copy is present (e.g. Turner syndrome)
  • Trisomy – the individual has three copies of a chromosome. Examples are:

Structural Chromosomal Abnormalities

Deletion mutations

Deletions are when part of the chromosome is missing. An example is cri du chat syndrome which is due to the deletion of the short arm of chromosome 5 (5p).

  • This is also known as 5p monosomy or partial monosomy.

Duplication mutations

Duplications are when a part of the chromosome is duplicated. An example is a subtype of Charcot-Marie-Tooth disease which occurs due to the duplication of a gene on chromosome 17.

Translocation mutations

Translocations are when a part of a chromosome has been transferred to another. This can be divided into:

  • Reciprocal translocation – portions from two different chromosomes have been exchanged
    • An example of this is the Philadelphia chromosome translocation in acute myeloid leukaemia where there is a reciprocal translocation between chromosome 9 and chromosome 22.
  • Robertsonian translocation – an entire chromosome has attached to another at the centromere. This only happens in acrocentric chromosomes (where the centromere is not in the middle and is found near the end of a chromosome) which are chromosomes 13, 14, 15, 21, and 22 in humans.
    • Although the individual has the same genetic material and may remain phenotypically intact, they now have 45 chromosomes. This leads to risks in their offspring, such as Down’s syndrome if the offspring inherit an extra copy of 21 attached to another chromosome.

Mosaicism

Chromosomal abnormalities may occur after conception and this results in only part of the body’s cells having the abnormality. This leads to a wide range of outcomes and features that are difficult to predict.

Author