MM 14-15 Genetics 1 Flashcards
Aneuploidy
The failure of homogenous chromosome to separate properly. Can include monoploid or trisomy. Occurs in all cells but has detrimental effects during meiosis in women or early on in development.
Mosaicism
When aneuploidy occurs in mitosis, creating a monosomy and trisomy cell lineage. Symptoms are usually less severe than de novo non-disjunction.
Down syndrome
Non-disjunction of chromosome 21 during meiosis. (trisomy).
1/650 live birth. Risk increases with age. 1/900 at age 30, 1/40 at age 40.
Non-disjustion in Meiosis I vs II
In meiosis 1, non-disjunction effects all of the 4 daughter cells. 2 have an extra chromosome and the other two lack a chromosome.
In meiosis 2, half of the cells are fine, but triploidy occurs in one cell and monoploid in the other.
Translocations
Translocations is the swapping of heterologous arms at places of genetic similarity. The mechanism for the breaking is not known and it is not related to crossing over and is not a mitosis/meiosis event.
Reciprocal translocation
A reciprocal translocation is when parts are 2 non homologous chromosomes are traded for one another. If balanced no genetic information is missing and there are no phenotypic manifestations. However, However, fertility issues are likely to arise. If unbalance, genes are cut causing the primary cause of lymphomas and leukemia.
Robertsonian translocation
Rather than a swapping of genetic information between chromosomes, non-homologous chromosome are joined. This usually happens on due to break near the centromere of acrocentric chromosomes. Imagine breaking the eraser off of two pencil and putting them together, end to end. Such a cell would have one fewer chromosome. Upon fertilization, 4/6 would have aneuploidy and 2/6 would have the full genome.
Cytogenetics
Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the chromosomes. It includes routine analysis of G-banded chromosomes, other cytogenetic banding techniques, as well as fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH).
Indications for prenatal cytogenetic testing:
- irregular ultrasound
- older mother
- history of miscarriage
- carrier with chromosomal abnormality
Indications for postnatal cytogenetic testing:
- dysmorphic features
- developmental delay
- clinical features
- history of miscarriage
- family history of chromosomal abnormalities
Detection of microdeletion syndromes
Many micro deletion syndromes have dysmorphic features. But deletion is usually too small for G-band karyotyping.
FISH works, but must be looking for a specific disorder.
Chromosomal micro array is the new gold standard for subtle insertion/deletions. Same resolution as FISH but entire genome can be scanned. Best for unexplained cases.
Consanguinity
Consanguinity is the property of being from the samekinshipas another person.
Why are there fewer autosomal dominant diseases?
Both recessive and dominant alleles are expressed within a genome. A heterozygous autosomal disease has effects that are strong enough to cause a disorder to be represented. Alternatively, a homozygous autosomal disease has such a strong impact that the person often doesn’t live to child bearing age. Therefore, most AD disorders only exist as heterozygous. Recessive diseases, however, have a smaller phenotypical representation and can be hidden within the genome and spread.
Familial hypercholesterolemia
An example of an autosomal dominant disease leading to excessive cholesterol. The heterozygous manifestation results in MI near age 30, while the homozygous results in MI during childhood.
Examples of Autosomal dominant diseases.
Polycystic kidney disease, neurofibromatosis, familial hypercholesterolemia.