Genetic Disorders and Terminology Flashcards
Familial hypercholerolemia
Mode of transmission, clinical features, name of gene
Autosomal DOMINANT
Deficiency of LDLR
-Example of haploinsufficiency
-Influenced by lifestyle factors
Huntington’s Disease
Mode of transmission, clinical features, name of gene
Autosomal DOMINANT
Example of gain of function of the protein
-Triplet repeat expansion disorder, displays anticipation
High penetrance, 90% of cases are adult onset
Myotonic Dystrophy
Mode of transmission, clinical features, name of gene
Autosomal DOMINANT
Gain of function at the mRNA level (3’ untranslated region)
-Triplet repeat expansion disorder, anticipation, and pleiotropy
Marfan Syndrome
Mode of transmission, clinical features, name of gene
Autosomal DOMINANT
FBN1
-Has both haploinsufficiency forms and dominate negative forms
Osteogenesis imperfecta
Mode of transmission, clinical features, name of gene
Autosomal DOMINANT
COL1A1 and COL1A2
-Brittle bone disease
-Has haploinsuffiency forms, and also dominant negative forms
Achondroplasia
Mode of transmission, clinical features, name of gene
Autosomal DOMINANT
FGFR3
-Example of gain of function, unregulated tyrosine kinase signaling
-Nearly 100% penetrance
Neurofibromatosis type I
Mode of transmission, clinical features, name of gene
Autosomal DOMINANT
NF1
-Example of AD because of loss of heterozygosity, NF1 as a tumor supressor gene
-highly penetrant but has variable expressivity. High allelic heterogeneity
Acute intermittent porphyria
Mode of transmission, clinical features, name of gene
AUTOSOMAL DOMINANT
-Heme synthesis deficiency
-Rare example of an enzyme deficiency that is autosomal dominant (most are recessive)
-AIP is dominant because of high cellular demand for heme
Type of haploinsufficiency
Cystic Fibrosis
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE
-CFTR gene, chloride channel
-highly penetrant
Sickle Cell Anemia
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE
-structural variant of the beta-globin protein in hemoglobin
-Glu6Val
Phenylketornuria
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE
-inability to degrade phenylalanine
-causes brain damage
-PAH gene
Tx: with diet lacking phenylalanine
Tay-Sachs Disease
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE
-Hexosaminidase A deficiency HEXA gene
-Lysosomal storage disease
Hemochromatosis
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE
-Delayed age of onset, and incomplete penetrance
-tendency to accumulate toxic amts of iron
Homocystinuria
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE
Build up of homocysteine
Galactosemia
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE
-Inability to degrade glacatose which is found in the breakdown of lactose
Alpha 1-antitrypsin deficiency
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE
-Leads to adult onset loss of lung elasticity and can cause liver damage in children
Severe combined immune deficiency (SCID)
Mode of transmission, clinical features, name of gene
Autosomal RECESSIVE OR X-Linked recessive
-**ADA **gene/Defect in the gamma chain for IL2RG (interleukin)
-d/t build up of adenosine
Good example of Locus Heterogeneity
Duchenne Muscular Dystrophy
Mode of transmission, clinical features, name of gene
X-Linked recessive
Sx: Enlarged calves, wasting of thigh muscles
Extremely low genetic fitness (most people with this disease will not be able to mate)-lethal
Becker Muscular Dystrophy
Mode of transmission, clinical features, name of gene
X-Linked recessive
Less severe mutation to DMD-will see some genetic fitness
Hemophilia A
Mode of transmission, clinical features, name of gene
X-Linked recessive
Deficiency of clotting factor VIII (involves inversions of an intron sequence-incorrect splicing)
Many types of mutations can result in Hemophilia A (allelic heterogeneity
What is an obligate carrier?
Obligate=must be a carrier
What is skewed X-inactivation?
In regards to Duchenne Muscular Dystrophy
Number of cells contain the active X chromosome with the mutation in DMD are large compared to the functional DMD gene resulting in some symptoms of DMD such as weakness
Rett Syndrome
Mode of transmission, clinical features, name of gene
X-dominant
1. Lethal in males
2. Appear normal (6 months) then lose brain function
Incontinentia Pigmenti
Mode of transmission, clinical features, name of gene
X-linked dominant
Sx: Manifests as rashes & blisters in early life, learning disability and retinal detachment
Variable expressivity in females (X-inactivation)
Lethal in males
Vitamin D resistant Rickets
X-linked dominant
Incomplete penetrance definition (reduced)
Not everybody with the mutation displays the phenotype
What does Variable Expression mean?
ALL EFFECTED
Some individuals are more effected than others
1. Random chance
2. Other genetic factors (gender)
3. Environmental exposure
Examples: Xeroderma pigmentosum (autosomal recessive), Premenapausal females in Homochromatosis
Definition of Pleiotropy
A disease causing mutation that affects more than 1 organ system
Examples: Marfan Syndrome, Osteogenesis imperfecta, CF
Locus Heterogeneity definition and example
VS
Allelic Heterogeneity
LOCUS: Mutations of different genes that cause the same disease phenotype
BRCA1/BRCA2=Breast cancer
ALLELIC: Different mutations on the SAME gene cause the disease
Neurofibromatosis
