MM 14-15 Genetics 1

Question 1

Aneuploidy

Answer 1

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.

Question 2

Mosaicism

Answer 2

When aneuploidy occurs in mitosis, creating a monosomy and trisomy cell lineage. Symptoms are usually less severe than de novo non-disjunction.

Question 3

Down syndrome

Answer 3

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.

Question 4

Non-disjustion in Meiosis I vs II

Answer 4

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.

Question 5

Translocations

Answer 5

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.

Question 6

Reciprocal translocation

Answer 6

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.

Question 7

Robertsonian translocation

Answer 7

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.

Question 8

Cytogenetics

Answer 8

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).

Question 9

Indications for prenatal cytogenetic testing:

Answer 9

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

Question 10

Indications for postnatal cytogenetic testing:

Answer 10

1. dysmorphic features
2. developmental delay
3. clinical features
4. history of miscarriage
5. family history of chromosomal abnormalities

Question 11

Detection of microdeletion syndromes

Answer 11

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.

Question 12

Consanguinity

Answer 12

Consanguinity is the property of being from the samekinshipas another person.

Question 13

Why are there fewer autosomal dominant diseases?

Answer 13

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.

Question 14

Familial hypercholesterolemia

Answer 14

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.

Question 15

Examples of Autosomal dominant diseases.

Answer 15

Polycystic kidney disease, neurofibromatosis, familial hypercholesterolemia.

Question 16

Autosomal dominant inheritance patterns and exceptions:

Answer 16

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.

Question 17

Variable expressivity

Answer 17

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.

Question 18

Haploinsufficiency

Answer 18

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.

Question 19

Dominant negative effect

Answer 19

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

Question 20

Loss of heterozygosity

Answer 20

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.

Question 21

Autosomal Recessive expression and inheritance patterns

Answer 21

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.

Question 22

Examples of autosomal recessive diseases

Answer 22

Sickle cell anemia, cystic fibrosis, phenylketonuria.

Question 23

Allele

Answer 23

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

Question 24

Reduced penetrance

Answer 24

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

Question 25

Examples of AD diseases

Answer 25

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.

Question 26

Example on mitochondrial inherited disease

Answer 26

Leber’s optic Neuropathy