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Chromosomal aberrations

Chromosomal aberrations are disruptions in the normal chromosomal content of a cell, and are a major cause of genetic conditions in humans, such as Down syndrome.



Euploidy is the condition of having a normal number of structurally normal chromosomes. Aneuploidy is the condition of having less than or more than the normal diploid number of chromosomes, and is the most frequently observed type of cytogenetic abnormality.

Aneuploidy (numerical aberration)

Monosomy: 1 chromosome is missing. Eg:Turner syndrome.( 45 X) Trisomy :1 extra chromosome is present. Eg: Downs syndrome. Tetrasomy : 2 extra chromosomes are present. 48 chromosomes, not compatible with life. Triploidy : 1 extra chromosome set of haploid genome is present. 69 chromosomes Tetraploidy : 2 extra chromosome set of haploid genome is present. 92 chromosomes.

(B) Human disorders due to chromosome alterations in autosomes (Chromosomes 1-22)

a. Patau syndrome (trisomy 13): serious eye, brain, circulatory defects as well as cleft palate. 1:5000 live births. Children rarely live more than a few months. b. Edward's syndrome (trisomy 18): almost every organ system affected 1:10,000 live births. Children with full Trisomy 18 generally do not live more than a few months.

Down syndrome

(trisomy 21): The result of an extra copy of chromosome 21.

Down syndrome affects 1:700 children and alters the child's phenotype either moderately or severely. Down syndrome is correlated with age of mother but can also be the result of nondisjunction of the father's chromosome 21. Prone to developing early Alzheimer's and leukemia

Characteristic facial features, short stature; heart defects , susceptibility to respiratory disease, shorter lifespan . Often sexually underdeveloped and sterile, usually some degree of mental retardation.

1. 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. Eg- Cri du chat (cry of the cat): A specific deletion of a small portion of chromosome 5; these children have severe mental retardation, a small head with unusual facial features, and a cry that sounds like a distressed cat.


Conti.. Eg: Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4. Features include Severe to profound mental retardation, microcephaly, seizures, hypotonia, and cleft lip and/or palate. Characteristic facial features, include strabismus, down-turned "fishlike" mouth, short upper lip, small chin, and cranial asymmetry.

Conti.. Eg: Jacobsen Syndrome: also known as 11q deletion, is a rare congenital disorder resulting from deletion of a terminal region of chromosome 11 It can cause mild mental retardation, a distinctive facial appearance, and a variety of physical problems including heart defects and a bleeding disorder.

Prader-Willi syndrome (PWS) is caused by the absence of segment 11-13 on the long arm of the paternally derived chromosome 15. It is characterized by mental retardation, decreased muscle tone, short stature, emotional lability and an insatiable appetite which can lead to life-threatening obesity. PWS When this same segment is missing from the maternally derived chromosome 15, a completely different disease, Angelman syndrome, arises.

2.Duplication: if the fragment joins the homologous chromosome, then that region is repeated
Eg: - Fragile X: the most common form of mental retardation. The X chromosome of some people is unusually fragile at one tip - seen "hanging by a thread" under a microscope. Most people have 29 "repeats" at this end of their X-chromosome, those with Fragile X have over 700 repeats due to duplications. Affects 1:1500 males, 1:2500 females.

3. Translocation: a fragment of a chromosome is moved ("trans-located") from one chromosome to another - joins a nonhomologous chromosome. The balance of genes is still normal but can alter phenotype as it places genes in a new environment. Can also cause difficulties in egg or sperm development and normal development of a zygote. There are two main types of translocations.


Segments from two different chromosomes have been exchanged. Individuals carrying such abnormalities still have a balanced complement of chromosomes and generally have a normal phenotype, but with varying degrees of subnormal fertility.

Reciprocal translocations

Nonreciprocal translocation
A Robertsonian translocation is a type of nonreciprocal translocation in which two nonhomologous acrocentric chromosomes break at their centromere following which the long arms become attached to a single centromere. The short arms also join to form a reciprocal product, which typically contains nonessential genes and is usually lost within a few cell divisions. They cause chromosomal deletions or addition and result in syndromes of multiple Downs syndrome.

4.Inversions: A portion of the chromosome has broken off, turned upside down and reattached, therefore the genetic material is inverted. If the inverted area includes the centromere it is called a pericentric inversion. If it does not, it is called a paracentric inversion.

(D) Nondisjunction of the sex chromosome (X or Y chromosome)

a. Klinefelters syndrome: 47, XXY males. 1:850 male births Normal intelligence. Rarely diagnosed before puberty Small stature, hypogonadism, lack of secondary male characteristics, gynecomastia The principle cause of male infertility due to reduced spermatogenesis

b. 47, XYY males: Individuals are somewhat taller than average and often have below normal intelligence. At one time (~1970s), it was thought that these men were likely to be criminally aggressive, but this hypothesis has been disproven over time.

c. Trisomy X: 47, XXX females.

1:1000 live births - healthy and fertile usually cannot be distinguished from normal female except by karyotype

d. Monosomy 45X (Turner's syndrome)

Incidence 1:3000 to 1: 8000 live births The only viable monosomy in humans Women with Turner's have only 45 chromosomes XO individuals are genetically female, however, they do not mature sexually during puberty and are sterile.

Conti. Short stature and normal intelligence. (98% of these fetuses die before birth) webbing of the neck, cardiovascular abnormalities, lack of secondary sex characteristics