MM 14-15 Genetics 1 Flashcards Preview

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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.



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 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 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:

1. irregular ultrasound
2. older mother
3. history of miscarriage
4. carrier with chromosomal abnormality


Indications for postnatal cytogenetic testing:

1. dysmorphic features
2. developmental delay
3. clinical features
4. history of miscarriage
5. 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 is the property of being from the same kinship as 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.


Autosomal dominant inheritance patterns and exceptions:

Vertical, both sexes have equal chances of being affected, 50% chance of child being affected (assuming the parent is heterozygous).

Exceptions: reduced penetrance (if disease does not exhibit itself fully in all people), de-novo mutations (rare), variable expressivity.


Variable expressivity

The extent to which a disease presents with varying intensity, often to do with differences in gene expression. An example is Huntingtons disease, arisen from autosomal dominant triplet disorder. The more triplets, the greater the expressivity and the earlier the onset of the disease.



Haploinsufficiency is a mechanism of action to explain a phenotype when a diploid organism has lost one copy of a gene and is left with a single functional copy of that gene. Haploinsufficiency is often caused by a loss-of-function mutation, in which having only one copy of the wild type allele is not sufficient enough to express the wild type phenotype. It occurs when an organism has a single functional copy of a gene, and that single copy does not produce enough product to display the wild type's phenotypic characteristics.

Haploinsufficiency is usually caused by an autosomal dominant disorder. It can be the result of copy number variation, a gene coding for an ineffective protein, or transcription factors causing reduced expressivity.


Dominant negative effect

When an abnormal protein interferes with the function of the protein coded by the normal allele.


Loss of heterozygosity

A person inherits one faulty allele but later in life undergoes a random mutation effecting the healthy allele. It is in this manner that many cells become cancerous.


Autosomal Recessive expression and inheritance patterns

Mutated recessive alleles do not create an impact that effects phenotype if heterozygous. Therefore, many people are unknowing carriers and so recessive disorders hid in the blood until reproduction brings together 2 mutated recessive allies.

While carriers may not show the full phenotype, upon closer examination they some subtle signs of the disease may exist.

Small families make it harder to assess pedigree. Multicultural mating has spread AR diseases.


Examples of autosomal recessive diseases

Sickle cell anemia, cystic fibrosis, phenylketonuria.



A copy of a gene. May vary slightly between father and mother.


Reduced penetrance

Refers to the proportion in people with a given genotype who show the phenotype


Examples of AD diseases

Huntington’s disease: CAG triplet repeat on HTT gene. Gradual neurological deterioration--loss of muscle control and mental capability.

Fragile X: CGG triplet repeat within the Fragile X mental retardation 1 (FMR1) gene on the X chromosome. Dysmorphia: long and narrow face, large ears, flexible fingers, and large testicles. Intellectual disability & behavioral issues.


Example on mitochondrial inherited disease

Leber's optic Neuropathy