- Genetic Causes :
- Aneuploidy : Too many or too few chromosomes , it is always associated with physical and/or mental developmental problems. It occurs at the time of fertilization .
- Trisomy : Instead of a pair, 3 chromosomes are present
- Monosomy : Instead of a pair single chromosome is present.
If the extra or missing chromosome is an autosome (chromosomes 1 to 22), the embryo may not implant or may stop normal development soon after implantation and undergo spontaneous abortion.
But chromosomes involving 13,18, 21, X or Y, embryo may implant and carry to term. eg
- Down syndrome – Trisomy -21 Three copies of chromosome
- Patau syndrome – Trisomy – 13
- Edward syndrome – Trisomy – 18
- Klinefelter syndrome – presence of an extra sex chromosome 47, XXY
- Turner Syndrome – missing a sex chromosome 45 , X
Structural Chromosome Abnormalities :
Translocations : In Translocations a piece of chromosome go and attached to a wrong chromosome. There are two types of structural chromosome abnormalities
- Robertsonian & Reciprocal Translocations
Robertsonaian Translocations :
A type of translocation exclusive to the acrocentric chromosomes (13,14,15,21 & 22), in which two chromosomes join at or near their centromeres . This is effectively a fusion between two chromosomes rather than an exchange of material as in reciprocal translocations. Oocyte and sperm from couple carrying Robertsonian translocation either contain balanced or unbalanced genetic material. In case of unbalanced translocation resultant embryo will have too many copies of one chromosome and too few copies of the other.
This results in too many or too few normal genes on a chromosome. It may lead to embryo death, miscarriage or live birth of an infant with substantial medical problems.
Uniparental disomy [UPD] & Robertsonain Translocations :
Genomic imprinting :
Differential expression of genes based on their parent of origin. Disrupted imprinting can give rise to birth defects testing for UPD can be done by comparing DNA from each parent to the DNA of the embryo.
Reciprocal Translocations :
It is a exchange of chromosomal material between the wrong chromosomes. If this exchange breaks a gene, person will have a genetic disease.
Chromosome Deletions :
Deletions are the loss of a chromosome segment resulting in an imbalance in the number of genes present. If the deletion removes genetic material, the individual will have a genetic disorder. eg. Cri du chat, prader-will and Angelman’s syndrome.
Chromosome inversions :
Inversions occur when a single chromosome breaks in two places and the material is reconstituted upside down. If the chromosome breaks and does not disrupt any gene, individual with an inversion are normal but if a gene sequence is altered the individual will have a genetic abnormality. eg. Leukemia [inversion of chromosome 16].
Conditions diagnosed by PGD :
Sex – linked disorders :
Genetic disorders caused by mutations in genes on the sex chromosomes [X,Y] are called sex linked disorders. Females have two X chromosomes, One inherited from each parents. Men have one X and one Y chromosome. Genes for most sex linked disorders are located on X chromosome, usually occurs in men. As men has only one X chromosome, so a single recessive gene on that X chromosome will cause the disease. Although the Y chromosome is the other half of the XY gene pair in the men, the Y chromosome does not contain most of the genes of the X chromosome. And therefore does not protect the men.
Dominant inheritance occurs when an abnormal gene from one parent is capable of causing disease even though the matching gene from the other parent is normal. The abnormal gene dominates the outcome of the gene pair .
For eg. Rett Syndrome, Incontinentia pigmentin, pseudohyper parathyroidism, vitamin D-resistant rickets
Recessive Inheritance occurs when both matching genes must be abnormal to produce disease. If only one gene in the pair is abnormal, the disease is not manifest or is only manifest mildly. Eg. Hemophilia, fragile X-syndrome, neuromuscular dystrophies.
Carrier - Some one has one abnormal gene (No symptoms) is called a carrier. A carrier can pass this abnormal gene onto his or her children. Eg. Cystic fibrosis