Chromosomal Abnormalities and Karyotypes

Human somatic cells contain 46 chromosomes. This is the diploid number and can be written as 2n.The 46 chromosomes are not actually 46 distinctly different units, but 23 pairs of homologous chromosomes. Each homologous pair is made up of one maternal and one paternal chromosome. Therefore 23 chromosomes came from the mother and 23 came from the father. Therefore, the haploid number (n) for humans is 23.Each homologous chromosome (homolog) carries information for the same genetic traits as it partner chromosome. The information for any particular trait is called a gene. The genes on the homologs are not necessarily identical. There may be variations in the genes. For example, the gene for earlobe shape may code for free earlobes on one chromosome and attached earlobes on the other chromosomes. These different forms of the same gene are called alleles.

Karyotypes are studies of chromosomes photographed while they are condensed in mitosis. The chromosomes are organized by size into their homologous pairs and studied. The pairs are matched by examining the size, arm lengths (centromere position) and banding patterns.

Chromosomal Abnormalities and Karyotypes

Chromosome Number and Homologous Chromosomes

Chromosomal Abnormalities and Karyotypes

Creating a Karyotype

The Normal Human Karyotype

The normal human karyotype is composed of SEVEN groups of chromosomes (A ­ G) plus thesex chromosomes (X and Y). The chromosomes are grouped according to size, position of the centromere and the characteristic banding pattern . The first seven groups are called the autosomes while the larger X and smaller Y chromosomes are called the sex chromosomes.

Chromosomal Abnormalities and Karyotypes

sister chromatids

non-sister chromatids

sex chromosomes

autosomes

homologs

Normal Male Karyotype

Chromosomal Abnormalities and Karyotypes

Diagnosing Syndromes with Karyotypes:Alterations in Chromosome NumberNondisjunction can occur when chromosomes fail to separate:

Anaphase I: homologs fail to separateAnaphase II: sister chromatids fail to separate

The result is that one gamete ends up with 2 copies of a chromosome and the other gamete ends up missing a chromosome.

If the gamete is fertilized, the result is aneuploidy (abnormal chromosome number). The frequency of nondisjunction is fairly high in humans, but the results are usually so devistating to the growing zygote that miscarriage occurs very early in the pregnancy. If the individual survives, they usually have a set of symptoms ­ a syndrome ­ caused by the abnormal dose of gene product from the extra or absent chromosome.

Chromosomal Abnormalities and Karyotypes

Trisomic cells (2n+1)Polyploidy results when the cells have one extra chromosome. There only 3 trisomies of autosomal chromosomes that result in a baby that can survive for a time after birth; the others are too devastating and the baby usually dies in utero.

Down Syndrome (Trisomy 21): The result of an extra copy of chromosome 21. Symptoms include developmental delay and distinct facial characteristics (e.g. skin fold at inner corner of eyes)

Edward's Syndrome (Trisomy 18): The result of an extra copy of chromosome 18. The infant will have multiple congenital abnormalities. In most cases life expectancy is about 3 months.

Patau Syndrome (Trisomy 13): The result of an extra copy of chromosome 13. The infant will have multiple congenital abnormalities. In most cases life expectancy is about 1 year.

Monosomic cells (2n­1)These cells have one missing chromosome. This type of aneuploidy is usually lethal except for the case where the X sex chromosome is missing.Turner's Syndrome (Monosomy XO): The result of a missing second sex chromosome, the cells contain only one copy of X. Individuals are both anatomically and physiologically female, but have rudimentary ovaries, no menstruation or ovulation.

Chromosomal Abnormalities and Karyotypes

Nondisjunction of the Sex Chromosomes (X or Y chromosome):

Klinefelter syndrome (47, XXY males): Male sex organs usually underdeveloped, resulting in reduced secondary sex characteristics.

Jacob's Syndrome (47, XYY males): Individuals are somewhat taller than average and may be at risk for learning disabilities and delayed motor skill development.

Trisomy X (47, XXX females): Usually healthy and fertile with no syndrome.

Multiple Sex Chromosomes: Individuals may also have multiple sex chromosomes (females XXXX, XXXXX and males XXXY, XXXXY)

Note: Turner's Syndrome (XO) is the only viable monosomy in humans.

Chromosomal Abnormalities and Karyotypes

Sometimes, chromosomes break, leading to 4 types of changes in chromosome structure:

Alterations in Chromosome Structure

Deletion Inversion

DuplicationTranslocation

Chromosomal Abnormalities and Karyotypes

Deletion: a portion of one chromosome is lost during cell division. That chromosome is now missing certain genes. When this chromosome is passed on to offspring the result is usually lethal due to missing genes.

Cri du Chat (Deletion on chromosome 5): "Cry of the Cat" A specific deletion of a small portion of chromosome 5. Individuals have severe developmental delay, a small head with unusual facial features, and a cry that sounds like a distressed cat.

Fragile X (Duplication X): One of the most common forms of developmental delay. The X chromosome appears fragile at one tip, as if "hanging by a thread". This results from an extremely high number of repeats at the telomere region.

Duplication: if the broken fragment joins the homologous chromosome, then that region is repeated.

Chromosomal Abnormalities and Karyotypes

Translocation: a fragment of a chromosome is moved (translocated) from one chromosome to another. The fragment joins a non­homologous chromosome. Although all of the genes are still present in the correct amounts (nothing has been gained or lost) the misplacement can have affects in the body.

Philadelphia Chromosome (Translocation of part of Chromosome 9 onto Chromosome 22): Individuals have increased risk of developing a form of Leukemia.

> Inversion: When a chromosome breaks and the piece of the chromosome turns upside down and reattaches itself. Inversions may or may not cause birth defects depending on their exact structure.