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Flashcards in MM 16-18 Deck (30):

Which occurs more? Loss of protein function mutation or gain of protein function mutation?

Loss of protein


Mutation nomenclature: R408W

Arginine (R) at codon 408 becomes Tryptophan (W).

R408X would mean that Arginine was replaced with a stop codon.

del means deletion


Monogenic disease

Single gene defect


Locus heterogeneity

A disease that can have a phenotype upon mutations on several different genes. Normally the disease is the result of complex pathways or structures.


Allelic heterogeneity mutation and examples

A disease that arises from a mutation on one specific gene. The disease phenotype does not arise from mutations on other genes. Mutations can still come from different places on the gene and have different severities, but only the same gene is always involved in the disease.

Cystic Fibrosis


Compound heterozygosity

Compound heterozygosity is the condition of having two heterogeneous recessive alleles at a particular locus that can cause genetic disease in a heterozygous state.

For example, both alleles might be mutated but at different locations.


Complex inheritance

A disease that may not show Mandelian inheritance patterns to to its polygenic complexity and environmental factors. Eg, cardiovascular disease.



Genetic predisposition for a disease due to mutations in many gene loci that each have a small contribution. Can be oligogenic or polygenic inheritance.



Epigenetics studies genetic effects not encoded in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors that switch genes on and off and affect how cells express genes. They may or may not be heritable.

Eg. Methylation or Acetylation, tagging of DNA or histone to change the expression of a gene.


Genomic imprinting

Genomic imprinting is the epigenetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed. If the allele from the mother is imprinted, then only the allele from the father is expressed. There are about 60 known genes that undergo imprinting.

Disease can come when a mutation occurs on the active gene while the other is silenced.


X-chromosome inactivation

Women do not produce twice as many X encoded proteins as men. This is because one of the X-chromosomes (random) on women is inactivated early in embryonic life. Heterochromatin on the inactivated chromosome is condensed so that it cannot be transcribed, called a Barr-body.


Intermediate effect

Biochemically affected but clinically not.


X-linked recessive

Most X-linked diseases. A disease that is variably expressed in females and fully expressed in males.

Diseases are characterized as XLR or XLD based on how many females are clinically affected.


X-linked dominant

A disease that is expressed clinically in most people who carry the mutant gene. (Very Few disorders exist).


Inheritance patterns of X-linked recessive

Complete absence of male to male transmission. Mainly males effected in the pedigree.

If a mother is a carrier, she will pass the disease on the half of her sons and half of her daughters will be carriers.

If a father has the disease, half of daughters will be carries and sons will be neither carriers or have the disease.


Examples of X linked recessive diseases

Duchenne muscular dystrophy


Inheritance patterns of X-linked dominant

Complete absence of male to male transmission.

Fathers with disease will pass it on to all of his daughters and none of his sons. Mothers with the disease will pass it on to half of her children.


Inheritance pattern of mtDNA

Disease passed on by mother only. All kids have a 50% of getting the disease.


Homoplasmy (think mtDNA)

Homoplasmy is when a cell has identical copies of mitochondrial DNA. When in normal and healthy tissues, all cells are homoplasmic. Homoplasmic mitochondrial DNA copies may be normal or mutated; however, most mutations are heteroplastic.

Note: mothers do not pass only one come of mtDNA to kids. The oocyte has many mitochondria, so it it much more likely for mutations to occur in only one or two of them.


Heteroplasmy (think mtDNA)

Heteroplasmy is when the mitochondria in a cell differ from each other. This would be the case if mtDNA mutated in a cell.


Six stages for genetic counseling

1. Collect information - med/family history
2. Counseling - inform of possible outcomes
3. Assessment - lab testing (+/- cascade tests)
4. Counseling - treatment/management
5. Referral - support group
6. Followup


For what type of diseases is genetic counseling appropriate for?

What is it not appropriate for?

-Chromosomal abnormalities
-Single gene mutations (but only 700/2500 single gene disorders have yet to be explained at a genetic level).

Not appropriate for common/complex disorders that may have locus heterogeneity or environmental factors.


Why do prenatal genetic diagnosis?

Age of mother
History of miscarriage
Family history of specific single gene disease.
Allows immediate treatment to prevent development issues.


Hardy Weinburg formula for population frequency:

p^2 + 2pq + q^2 = 1

p^2 = population of non carriers (AA)
2pq = population of carriers (Aa)
q^2 = population of diseased (aa)


Fragile X Syndrome

Symptoms often include mild to moderate intellectual disability. Physical features include a long and narrow face, large ears, flexible fingers, and large testicles.

Fragile X syndrome is typically due to the expansion of the CGG triplet repeat on the X Chromosome. This results in a failure to express the fragile X protein, which is required for normal neural development. Depending on the length of the CGG repeat, an allele may be classified as normal (unaffected by the syndrome), a premutation (at risk of fragile X associated disorders), or full mutation (usually affected by the syndrome). Permutations can get passed on and expanded to full mutations.


Huntington's Disease

The Huntington's disease triple repeat mutation that is genetically dominant and almost fully penetrant.


Multifactorial Inheritance

A complex polygenic disease but the presence or absence of phenotype depends on environmental factors.


Genomic Screening tests in Ireland (newborn bloodspot)

Most treatable AR diseases that need to be detected early.

Maple Syrup Urine Disease
Cyctic Fibrosis
Congenital hypothyroidism



An invasive prenatal test.

Withdrawal of amniotic fluid during early second trimester.

Can be used for karyotyping, DNA analysis, protein and enzyme assessment.


Chorionic Villus sampling

An invasive prenatal test.

8-10 weeks.