Genetics - Final - Diseases and Conditions

davidwurbel7's version from 2015-04-22 03:17


Question Answer
A fatal neurodegenerative disease affecting 1 to 2% of the U.S. population. The more common form with late onset after age 60 shows no obvious mendelian inheritance pattern but does show familial aggregation and an elevated relative risk ratio typical of complex inheritance.Alzheimer Disease
The epsilon 4 allele of the apolipoprotein E (APOE) gene is clearly a predisposing factor that increases the risk for developmentAlzheimer Disease
The forebrain, overlying meninges, vault of the skull, and skin are all absent. Most infants are stillborn and two thirds of affected infants are femaleAnencephaly
Inherited as a single-gene disorder but more commonly is a sporadic occurrence in some families and demonstrates some degree of familial aggregation without an obvious mendelian inheritance pattern in others.Cleft Lip and Palate
One of the most common congenital malformations. Originates as a failure of fusion of the frontal process with the maxillary process at about the 35th day of gestation. Maternal smoking is a known risk factor. Nonsyndromic form can beCleft Lip and Palate
Affects 1 in 5,000 newborns; males have a 2 to 4-fold higher risk. Complete absence of some or all of the intrinsic ganglion cells in the colon, resulting in severe constipation, symptoms of intestinal obstruction, and massive dilatation of the colon (megacolon)Hirschsprung Disease (HSCR)
Autosomal dominant, autosomal recessive and multifactorial modes of possible inheritance. A developmental abnormality of the parasympathetic nervous system in the gut, aganglionic colon is incapable of peristalsis. Relative risk ratio for sibs is very high (λs~200), but MZ twins do not show perfect concordance. May involve mutations in many different genes (sometimes requiring more than one). RET (receptor tyrosine kinase), RET ligand GDNF (glial cell line-derived neurotrophic factor), EDNRB (endothelin B receptor) and its ligand endothelin3 (EDN3)Hirschsprung Disease (HSCR)
Venous or arterial clots form inappropriately and cause life-threatening complications.Hypercoagulable States
Clots form in the venous system of the brain causing catastrophic occlusion of cerebral veins; the factor V Leiden (FVL) and prothrombin 20210G>A mutations are also involved with deep venous thrombosis of the lower extremities seen in 1 in 1,000 individuals per year with mortality of up to 10%, primarily due to pulmonary embolus, depending on age and the presence of other medical conditions.Idiopathic Cerebral Vein Thrombosis
A form of retinal degeneration, the disease phenotype requires that the affected individual is heterozygous for two rare mutations in two different unlinked genes without the influence of any known environmental factors. Having the two mutated genes is sufficient to cross a threshold of cell damage, photoreceptor death, and loss of vision. Patients heterozygous for mutations in both the ROM1 and peripherin photoreceptor membrane proteins will develop the disease.Retinitis Pigmentosa
Among North American whites, this is the second most common chronic disease of childhood, increasing in prevalence from 1 in 2,500 at 5 years of age to 1 in 300 at 18 years of age.Type 1 Diabetes Mellitus/ Insulin-Dependent Diabetes Mellitus (IDDM)
Usually caused by autoimmune destruction of islet Beta cells in the pancreas. Loss of insulin reserve occurs during a few to many years. The earliest sign of abnormality is the development of islet autoantibodies when blood glucose concentrations, glucose tolerance (ability to maintain normal blood glucose levels after ingestion of sugar), and insulin responses to glucose are normal.Type 1 Diabetes Mellitus/ Insulin-Dependent Diabetes Mellitus (IDDM)
Followed by a phase of decreased glucose tolerance but normal fasting blood glucose concentration. With continued loss of beta cells, fasting hyperglycemia eventually develops but sufficient insulin is still produced to prevent ketosis; during this period, patients have non-insulin-dependent diabetes mellitus. Eventually, insulin production falls below a critical threshold, and patients become dependent on exogenous insulin supplements and have a propensity to ketoacidosis.Type 1 Diabetes Mellitus/ Insulin-Dependent Diabetes Mellitus (IDDM)
Autoimmune destruction of islet beta cells, Polydipsia-excessive or abnormal thirst; polyuria-excessive secretion of urine are signs ofType 1 Diabetes Mellitus/ Insulin-Dependent Diabetes Mellitus (IDDM)
Major genetic factor -> MHC class II locus (HLA-DR3 or HLA-DR4). The DQβ1*0201 allele, which segregates with DR3, and DQβ1*0302, which segregates with DR4, are the primary susceptibility alleles for what diseaseType 1 Diabetes Mellitus/ Insulin-Dependent Diabetes Mellitus (IDDM)
Usually results from a genetic susceptibility & subsequent environmental insult and only very rarely from an environmental insult or a genetic mutation alone. Usually manifests in childhood or adolescence and is a result of the autoimmune destruction of the beta cells of the pancreas which normally produce insulinType 1 Diabetes Mellitus/ Insulin-Dependent Diabetes Mellitus (IDDM)
PTPN22-protein tyrosine phosphatase, non-receptor type 22 (lymphoid), is a protein which in humans is encoded by the PTPN22 gene. The common 1858T (rs2476601) nonsynonymous single nucleotide polymorphism located in the PTPN22 gene has been associated with a range of autoimmune disorders, includingType 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus (SLE) and Graves' disease.
Failure of fusion of the arches of the vertebrae with varying degrees of severity, typically in the lumbar regionSpina Bifida
Which disease is associated with HLA-B27Anklosing Spondylitis
Chronic inflammatory disease of the spine and sacroiliac joints Anklosing Spondylitis
Post-axial polydactyly-Congenital heart defects (most commonly an atrial septal defect producing a common atrium, occurring in 60% of affected individuals)-Prenatal tooth eruption-Fingernail dysplasia-Short-limbed dwarfism-Short ribs-Cleft palate-Malformation of the wrist bones (fusion of the hamate and capitate bones).Ellis-Van Creveld (EVC) Syndrome
The disease ranges from mild to severe, and typically occurs only in some second or subsequent pregnancies of Rh- women where the fetus's father is Rh+, leading to a Rh+ pregnancy. During birth, the mother may be exposed to the infant's blood, and this causes the development of antibodies, which may affect the health of subsequent Rh+ pregnancies.Hemolytic Disease of the Newborn
Mutant HFE gene (Cys282Tyr) in linkage disequilibrium with HLA-A*0301Hemochromatosis
A common autosomal recessive disorder of iron overload -> have homozygous mutation in a gene which is involved with iron transport or metabolism in the intestineHemochromatosis
A condition marked by the deposit of bile pigments in the nuclei of the brain and spinal cord and by degeneration of nerve cells that occurs usually in infants as a part of the syndrome of erythroblastosis fetalisKernicterus
Primary susceptibility alleles are DQB1 which segregate with HLA-DR3 & HLA-DR4Type 1 Diabetes
Presenting in adolescence or young adulthood, most often affects segments of the gastrointestinal tract, such as the terminal small intestine (ileum) and portions of the ascending colon; but it can occur anywhere within the digestive tract, with granulomatous inflammation that penetrates the wall of the intestine and produces narrowing and scarring.Crohn Disease (CD)
Onset is usually insidious with a history of nocturnal abdominal pain, diarrhea, and gradual weight loss. Multiple granulomas in the wall of the small intestine.Crohn Disease (CD)
Which disease is associated with NOD2 (“nucleotide-binding oligomerization domain containing 2”) proteinCrohn Disease
IBD1 locus, which disease is associated with it and have a locus with highest score (> 5) determined to show linkageCrohn Disease
Significant linkage disequilibrium was observed between mutant CF alleles (∆F508) and a particular haplotype. What disease is thisCystic Fibrosis
Patients have pancreatic insufficiency, severe progressive lung disease, and congenital absence of the vas deferens in malesCystic Fibrosis
(∆F508)-3-bp deletion removes a phenylalanine at position 508 found in ~70% of all mutant CF genes in northern European populationsCystic Fibrosis
A complex genetic disease with no discernable mendelian inheritance pattern that affects the gastrointestinal tract primarily in adolescents and young adultsInflammatory Bowel Disease (IBD)
Use of LD revealed 3 SNPs in LD with the disease which mapped to exons of the NOD2 gene -> variants strongly associated with diseaseInflammatory Bowel Disease (IBD)
Is an inflammatory disorder that involves tender, red bumps (nodules) under the skin which is most common on the shins, but it may also occur on other areas of the body (buttocks, calves, ankles, thighs, and arms). The lesions begin as flat, firm, hot, red, painful lumps approximately an inch across. Within a few days they may become purplish, then over several weeks fade to a brownish, flat patch.Erythema Nodosum


Question Answer
Degenerative disease of the retina that causes progressive blindness in association with abnormal retinal pigmentationRetinitis Pigmentosa
Is a condition that causes large, painful sores (ulcers) to develop on your skin, most often on your legs.Pyoderma Gangrenosum
Is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer. The underlying cause of the inflammation is believed to be autoimmunity; and more than 80% of those with this also have ulcerative colitis. The definitive treatment is liver transplantation.Primary Sclerosing Cholangitis (PSC)
Autosomal Recessive disorder where the β-chain has substitution at sixth amino acid from glutamic acid to lysine -> less soluble than Hb A and tends to crystallize in RBCs causing a mild hemolytic disorderHb C
Autosomal Dominant. β-chain Phe42Ser. Unstable hemoglobin with substitution of the conserved phenylalanine with serine allowing heme to drop out of its pocket causing hemoglobin to precipitate, also has low oxygen affinity leading to cyanosisHb Hammersmith
Loss of 3 α genes -> moderately severe anemia + splenomegalyHb H (b4)
Autosomal Dominant. β-chain His92Tyr. Example of a β-chain methemoglobin where oxidized heme iron is incapable of reversible oxygenation; causes a heterozygote to be cyanotic (blue/purple)Hb Hyde Park (a Hb M)
Autosomal Dominant. β-chain Asp99Asn. Gain of function mutation that “locks” hemoglobin into the relaxed structure with high oxygen affinity causing polycythemia (an abnormal increase in the number of circulating red blood cells)Hemoglobin Kempsey
Impairment of the perinatal switch from γ-globin to β-globin synthesisHereditary Persistence of Fetal Hemoglobin
A benign condition because the remaining γ gene or genes remain active after birth and Hb F (α2γ2) compensates for the absence of Hb A Hereditary Persistence of Fetal Hemoglobin
No α-globin chains -> infants have severe α-thalassemia and high levels of Hb Bart’s -> homotetrameric with γ4 composition is an ineffective oxygen carrier, primarily seen among Southeast Asians. Results in severe intrauterine hypoxia, infants are born with massive generalized fluid accumulation -> invariably causes stillbirth or neonatal deathHydrops Fetalis
Novel property mutation due to amino acid substitution -> hemoglobin chains aggregate when deoxygenated and form polymeric fibers that deform RBCsSickle cell disease
Autosomal Recessive Disorder where Glutamic Acid (GAG) is replaced by Valine (GTG) which results in a transversionSickle cell disease
Caused by homozygosity of the mutation is a severe autosomal recessive hemolytic condition; heterozygotes are generally clinically normal and confers the heterozygote advantage of resistance to malaria. The vaso-occlusive crisis is caused by abnormal red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischemia, pain, necrosis and often organ damage.Sickle cell disease
Patients with this disease generally present in the first two years of life with anemia, failure to thrive, splenomegaly, repeated infections, and dactylitis (the painful swelling of the hands or feet from occlusion of the capillaries in small bones). Sickle cell disease
Impairs the production of β-globin alone -> accounts for the great majority of patients. Result of many different types of molecular abnormalities, predominately point mutations in the β-globin gene -> most lead to a decrease in the abundance of β-globin mRNA. Include promoter mutants, RNA splicing mutants (most common), mRNA capping or tailing mutants, and frameshift or nonsense mutations. Nonfunctional mRNAs-have premature stop codons due to single nucleotide substitution (Gln39Stop) or single-base pair deletion at codon 16 -> cause βo thalassemiaSimple β-Thalassemia
Which disorder can make the bone marrow expand, which causes bones to widen. This can result in abnormal bone structure, especially in the face and skull. Bone marrow expansion also makes bones thin and brittle, increasing the risk of broken bones. Skeletal changes are due to expansion and invasion of erythroid cells in the bone marrow, which widens the marrow spaces, attenuates the cortex, and produce osteoporosis.Thalassemias
Autosomal Recessive Disorders. Heterogeneous group of diseases in which mutations reduce the synthesis or stability of either the α-globin or β-globin chain. The chain produced at the normal rate is in excess and eventually precipitates to form occlusions (Heinz bodies), damaging the membrane, and causing premature RBC destructionThalassemia
Individuals with two β-thalassemia alleles -> this condition is characterized by severe anemia needing lifelong medical management (also called Cooley’s anemia)Thalassemia major.
Seen in carriers of one β-thallassemia allele -> have hypochromic, microcytic RBCs and may have slight anemiaThalassemia minor
What major metabolites accumulates due to deficiency in GlucocerebrosidaseGlucocerebroside
What major metabolites accumulates due to deficiency in Hexosaminidase-Alpha SubunitGM2 Gangliosidosis