Genetics Flashcards
Familial Hypercholestoremia
Autosomal dominant leading to LDL deficiency
Huntington’s Disease
Autosomal dominant-triplet repeat disorder. Gain of function mutation.
Myotonic Dystrophy
Autosomal Dominant. DMPK mutation, highly pleiotropic.
Achondroplasia
Autosomal dominant. Deficient in FGFR3 (growth factor). Relatively normal life span.
Marfan’s Syndrome
Mutation in Fibrillin-1 gene. Autosomal dominant. Pleiotropic. Dominant negative mutation.
Osteogenesis Imperfecta
Autosomal dominant. Brittle bone syndrome.
Neurofibromatosis
Autosomal Dominant. Mutation in NF-1 gene, NF-1 codes for nuerofibrillin which is a tumor suppressor gene. Has variable expressivity-some have cafe au lait spots and other have small tumors all over the body, and Lisch nodules in the eyes. Allelic heterogeneity.
Acute Intermittent Porphyria
Autosomal dominant. Causes an enzyme deficiency, one of the only AD that do that.
Cystic Fibrosis
Mutation in the CFTR gene.
Sickle Cell Anemia
Autosomal Recessive
Phenylketonuria (PKU)
Autosomal Recessive
Tay Sachs Disease
Hexosaminidase A deficiency. Autosomal recessive.
Congenital Deafness
Autosomal recessive
Hemochromatosis
Build up of iron in the body. Autosomal recessive. Delayed age of onset. Allelic heterogeneity.
Alkaptonuria
Delayed age of onset. Autosomal recessive.
Homocystinuria
Autosomal recessive.
Galactosemia
Autosomal recessive
Alpha 1-antitrypsin deficiency
Autosomal recessive
SCID due to adenosine deaminase deficiency
Autosomal recessive
What is the molecular basis for most autosomal recessive disorders?
Loss of function mutations (e.g., enzyme deficiencies) is
Pseudo-autosomal dominant disorder
An autosomal recessive condition that is present in two or more generations in the family, looking like its following a dominant inheritance pattern. Seen when there is a high carrier frequency (sickle cell) and high incidence of consanguinity
X-linked recessive disorders (female)
Very rare in the population, color blindness is the only known one.
X-linked recessive
More common in males, skipping generations is common, fathers give disease allele to carrier daughters who give to affected sons. No male to male transmission.
Duchenne Muscular Dystrophy
Severe form, early on set, short life span. Low genetic fitness so men who have it don’t usually live long enough to pass it on. Muscle is replaced by adipose. Due to loss of the dystrophin protein. X-linked recessive.
Becker Muscular Dystrophy
X-linked recessive. Milder form of DMD, not usually seen until after 25 years of age.
Glucose-6-phosphate dehydrogenase deficiency
X-lined recessive. Hemolytic anemia upon ingestion of primaquine, sulfa drugs.
Hemophilia A and B
Deficiency of clotting factor VIII resulting in increased bleeding after minor trauma. Most serve cases involve inversion of intron sequences. Allelic heterogeneity
Lesch-Nyhan nSyndrome
HGPRT deficiency. Leads to hyperuricemia, gout, and self mutilation. X-linked recessive.
Red-green color blindness
X-linked disease. Seen in males and females (more common in males).
X-Linked SCID
Defect in SCIDX1 gene. X-linked recessive. Defect in gamma receptor which causes the T-cells to be unable to mature, leading to lack of Bcell function.
X-linked Dominant
Skipping of generations is not common, more females than males, no male to male transmission,affected male gives disease to all his daughters. Variable expressivity due to X inactivation.
Rhett Syndrome
Lethal in males. X linked dominant. Leads to hand wringing and shrinking head in females.
Incontinentia Pigmenti
X linked dominant. Males dies, females get tastes and blisters that become marble cake appearance later on.
Vitamin D Resistant Rickets
X linked dominant.
Leber Hereditary Optic Neuropathy
Mitochondrial disease. Progressive blindness around 20-30 years.
MELAS
Mitochondrial encephalopathy, lactic acidosis, and stroke like episodes
MERRF
Myoclonic epilepsy with ragged red muscles fibers. Mitochondrial inheritance.
The triplet repeat disorders
Huntingtons, myotonic dystrophy, and fragile X.
Retinitis Pigmentosa
Digenic disorder. Leads to progressive visual impairment. Results in a mutation in two independent genetic loci.
Imprinting
Certain gene is methylated which silences the gene, making the other one active. Some genes are only active when transmitted by the mother or father.
Prader Willi
Caused by micro deletion on paternal chromosome or maternal uniparental Disomy. Absence of SNRPN.
Angelman Syndrome
Deletion of maternal UBE3a gene or uniparental Disomy of SNRPN.
Fragile X
Triplet repeat on X chromosome on the 5’ end of the FMR1 gene, resulting in methylation which silences the gene. Results in learning disabilities, elongated face, prominent ears, and macro orchidism. Shows anticipation and is worse when it comes from mom.
Linked
Genes are said to be linked when they are arranged on the same chromosome, close enough that they have a recombination frequency of less than 50%
