Genetics - Final - Part 2

davidwurbel7's version from 2015-04-22 04:02


Question Answer
Disease due to deletion of a-globin genesα-Thalassemias
Two functional α genes (α-/α– or αα/--) -> results in mild anemia and microcytosis (decrease in the size of red blood cells)α-Thalassemia trait
Group of hemoglobinopathies resulting from a reduction in the abundance of β-globinβ-Thalassemias
Treatment for what disorder includes blood transfusions, iron chelation, prompt treatment of infection, and, frequently, splenectomy. Cure is possible by bone marrow transplantation. β-thalassemia
Onset of this disorder is not apparent until 2 to 6 months after birth. Usually due to single-base pair substitutions (point mutations) rather than deletions in one of the globin genesβ-Thalassemias
No Hb A presentβo Thalassemia
Nonfunctional mRNAs-have premature stop codons due to single nucleotide substitution (Gln39Stop) or single-base pair deletion at codon 16. This causesβo Thalassemia
If only 10 to 30% of Hb A is detectableβ+ Thalassemia
Caused by large deletions that remove the β-globin gene plus one or more other genes-or the LCRComplex Thalassemias
Some deletions within the b-globin cluster do not cause thalassemia but result in the phenotype termed the Hereditary persistence of fetal hemoglobin (HPFH). What type of thalassemia is this consideredComplex Thalassemias
Alternate sites that are not normally used by the spliceosome when the correct site is availableCryptic splice sites
Most common forms of α-thalassemia are the result ofDeletions (ZF deletion on Chromosome 16)
Mutations in the conserved GT dinucleotide at the 5’ intron donor site or AG at the 3’ intron acceptor site -> results in complete loss of splicingGroup 1, Splice junction mutations
Leads to an activated cryptic site that competes with the normal siteGroup 2, intron mutations
Mutations in the open reading frame that activate a cryptic splice site in an exonGroup 3, coding sequence changes that also affect splicing
α2β2Hemoglobin A (Hb A)
The two most conserved amino acids in the hemoglobin are shown atHistidine (His) 92 & Phenylalanine (Phe) 42
Normal plasma phenylalanine level<1 mM (1 mg/dl)
Levels of plasma phenylalanine level in PKU patients2-3 mM (6 to 80 mg/dl, usually > 30 mg/dl)
How long after birth of a new born can they be screened for PKU24 hours (The test is preferably not done before 24 hours of age as the phenylalanine level in PKU increases after birth).
This disorder damages the tiny air sacs (alveoli) in the lungs. When the alveoli are damaged, the lungs aren't able to expand and contract well enough for the person to breathe normally. Patients may feel short of breath, and they may cough or wheeze. As the lungs deteriorate, many patients develop lung diseases, such as emphysema, asthma, or chronic bronchitis. Symptoms include shortness of breath, wheezing, rhonchi, and rales. The patient's symptoms may resemble recurrent respiratory infections or asthma that does not respond to treatment.α1-Antitrypsin (α1AT) Deficiency
Individuals with this disorder may develop emphysema during their thirties or forties even without a history of significant smoking, though smoking greatly increases the risk for emphysema. Also causes impaired liver function in some patients and may lead to cirrhosis and liver failure (15%). It is a leading cause of liver transplantation in newborns.α1-Antitrypsin (α1AT) Deficiency
The function of the _______ is to bind the ganglioside substrate and present it to the enzyme NANA, N-acetyl neuraminic acid.Activator Protein
Different alleles of a single gene can be associated with phenotypes of variable severity. Mutations in the same gene have different effectsAllelic Heterogeneity
What is the mode of inheritance for I-Cell DiseaseAutosomal Recessive
What is the mode of inheritance of Phenylketonuria (PKU)Autosomal Recessive
What is the mode of inheritance of α1-Antitrypsin (α1AT) DeficiencyAutosomal Recessive
What is the mode of inheritance for HomocystinuriaAutosomal Recessive
What's the main body system that is affected by PKUCentral Nervous System (Brain)
α1AT deficiency is an example of an inherited___________which occurs when a mutation causes the shape or size of a protein to change in a way that predisposes it to self-association and tissue disposition.Conformational Disease
Classic homocystinuria is due to defectiveCystathionine Synthase.
Deficiency in this causes megaloblastic anemia, developmental delay, and failure to thriveDefects in Cobalamin metabolism
What major metabolites accumulates due to deficiency in α-L IduronidaseDermatan Sulfate & Heparan Sulfate
What major metabolites accumulates due to deficiency in L-Iduronosulfate SulfataseDermatan Sulfate & Heparan Sulfate
Individuals with the Z/Z genotype of α1-Antitrypsin (α1AT) Deficiency have a decreased life expectancy which is exacerbated by smoking. This is an example of ________ where the “environment” affects the phenotype of a genotype.Ecogenetics
Although α1AT inhibits a wide spectrum of proteases, it’s principal role is to bind and inhibit ________, particularly released from _______in the lower respiratory tract which can disrupt connective tissue. Elastase, Neutrophils
What are the cofactors for methionine synthaseFolate and Vitamin B12
What's the best treatment for PKUFood Modification (PAH free foods-MEATS)
What kind of mutation and what exon is the mutation found in that is seen in hexosaminidase A. This leads to no detectable Hex A protein is made, accounting for the complete enzyme deficiency observed in these infantile-onset patients.Frameshift Mutation (Exon 11)
Deficiency in GlucocerebrosidaseGaucher Disease
Other genes with overlapping biological activities are expressed in a tissue and lessen the impact of the loss of function of the mutant gene to a subclinical level.Genetic Redundancy
Although housekeeping proteins are expressed in most or all tissues, genetic diseases that affect these proteins rarely cause pathological changes in every tissue. Clinical effects of mutations in housekeeping proteins are frequently limited to one or a few tissues for at least two reasonsGenetic Redundancy & Specialty Function
Present in virtually every cell -> have fundamental roles in the maintenance of cell structure and functionHousekeeping Proteins
Mutations in different genes may produce similar, but often distinguishable, phenotypes. Mutations in different genes have the same effectLocus Heterogeneity
What are the primary organs affected by α1-Antitrypsin (α1AT) DeficiencyLung & Liver
One molecular explanation for the effect of smoking is that the active site of α1AT, at ____, is oxidized by both cigarette smoke and inflammatory cells, thus reducing its affinity for elastase by 2,000-fold.Methionine 358
In methylene-H4-folate reductase defects, the decrease in methyl-H4-folate impairs the function ofMethionine Synthase.
Both Classic PKU & hyperphenylalanemia result from a variety of mutations in the PAH locus; in those cases where a patient is heterozygous for two mutations of PAH (i.e. each allele has a different mutation), which mutation will predominateMilder Mutation
Mutations in a separate gene causes the same mutation in another gene to have different effectsModifier Genes
Diseases due to different enzymes that function in the same area of metabolism (i.e. mucopolysaccharidoses).Phenotypic Homology
The α1AT protein belongs to a major family ofProtease Inhibitors, the serine protease inhibitors or serpins.
What is the four base insertion in the Hex A gene and what kind of mutation does it leads toTATC & Frameshift Mutation
There are four other genes besides PAH deficiency that can cause PKU. What are they involved in, which is a cofactor of phenylalanine hydroxylase (PAH).The production of Tetrahydrobiopterin (BH4)
Produced in one or in a limited number of cell types -> have unique functionsTissue-Specific Specialty Proteins
Besides PAH, the BH4 is also required as a cofactor forTyrosine & Tryptophan hydroxylases in the synthesis of catecholamines (NE, E) and serotonin.
What is the cofactor for cystathionine β-synthaseVitamin B6 (pyridoxal phosphate)
What is the mode of inheritance for Hunter SyndromeX-link Recessive
Which allele is common in α1-Antitrypsin (α1AT) DeficiencyZ allele (Glu342Lys)
What percentage of Duchenne Muscular Dystrophy or Becker Muscular Dystrophy is due to gene deletion60%
Which Apolipoprotein E (APOE) allele has a protective function in Alzheimer disease ε2
Which Apolipoprotein E (APOE) allele is a major risk factor for developing Alzheimer disease ε4