Genetics Block 3 (Lectures 22-25 Pt.1)

cikobopi's version from 2015-07-20 02:32


Question Answer
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
What major metabolites accumulates due to deficiency in GlucocerebrosidaseGlucocerebroside
What major metabolites accumulates due to deficiency in Hexosaminidase-Alpha SubunitGM2 Gangliosidosis
Deficiency in the enzyme cystathionine β-synthaseHomocystinuria
Dislocation of the lens, Mental retardation, Osteoporosis, Long bones, tight bones, Thromboembolism of the veins and arteries. Homocystinuria
Disease that can be due to a deficiency of methionine synthase, and cofactor deficiencies.Homocystinuria
Some disorders directly affect methyl-B12 formation. Cobalamin intestinal absorption is abnormal in some patients. Other patients have abnormalities in the major extracellular transport protein, transcobalamin II. Homocystinuria
Vitamin B6 (pyridoxal phosphate, Vitamin B12 & Folate deficiencies can lead toHomocystinuria
Present in virtually every cell -> have fundamental roles in the maintenance of cell structure and functionHousekeeping Proteins
What TWO diseases results from deficiency in alpha-L-Iduronosulfate SulfataseHurler Syndrome (MPS 2 ) & Scheie Syndrome
Skeletal changes, hepatosplenomegaly, coarse facies, hearing loss, clear eyesHunter Syndrome
Corneal clouding, skeletal changes, hepatosplenomegaly, coarse facies, hearing loss, profound mental retardation, linear growth stops at 3 years old and death before the age of 10 years due to cardiorespiratory failureHurler Syndrome
Deficiency in Alpha-L IduronidaseHurler Syndrome (MPS 1 H)
In some cases, mutations in PAH result in a phenotypically mild form of PKU calledHyperphenylalanemia
Unusual facial features, Skeletal changes, Severe growth retardation, Mental retardation, Many of the acid hydrolases are found in excess in body fluids, Affected children typically survive for only 5 to 7 years I-Cell Disease
Mannose 6-phosphate deficiencyI-Cell Disease
Loss of Glycosylation is seen in what diseaseI-Cell Disease
Golgi-specific N-acetylglucosamine-1- phosphotransferase deficiency leads to a defect in protein traffickingI-Cell Disease
Defect in the enzymes that end up in the lysosome, that are targeted by the addition of mannose subunits that get phosphorylated.I-Cell Disease
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
Microcephaly, mental retardation, growth impairment, and heart malformations.Maternal Phenylketonuria
What kind of anemia can beseen in homocystinuriaMegaloblastic Anemia
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
Loss of of this enzyme results in mental retardation, organ damage, unusual posture, and in cases of maternal PKU, can severely compromise pregnancy. Phenylalanine Hydroxylase (PAH)
What converts phenylalanine to tyrosine by hydroxylating the phenolic ringPhenylalanine Hydroxylase (PAH)
Is due to the absence of phenylalanine hydroxylase (PAH) activity in the liver (LIVER is NOT damage), but the brain is damaged by the high blood levels of phenylalaninePhenylketonuria (PKU)
Damages the developing central nervous system in early childhood and interferes with the functioning of the mature brain. Developmental delay apparent in infancy, microcephaly, seizures, hyperactivity, and behavioral disturbances.Phenylketonuria (PKU)
Caused by mutations in both alleles of the PAH gene on chromosome 12Phenylketonuria (PKU)
In PKU, some phenylalanine is metabolized to ________ which is excreted in the urine causing a musky smell in the diaperPhenylpyruvic acid (a keto acid)
The α1AT protein belongs to a major family ofProtease Inhibitors, the serine protease inhibitors or serpins.
Mutation of the HexB gene, and production of a defective β- subunit, leads to inactivation of both hexosaminidase A and B activity. This disease is indistinguishable from Tay-Sachs diseaseSandhoff Disease
What is the four base insertion in the Hex A gene and what kind of mutation does it leads toTATC & Frameshift Mutation
Deficiency in Hexosaminidase-Alpha SubunitTay-Sachs Disease (GM2 Gangliosidosis)
A prominent red fovea centralis surrounded by a pale macula is found inTay-Sachs disease (Cherry-red spot in the retina)
The effects of neuronal cell death can be seen directly in the form of the so-called cherry-red spot in the retina.Tay-Sachs Disease
Lower motor neuron dysfunction and ataxia due to spinocerebellar degeneration, but unlike the infantile disease, vision and intelligence usually remain normal, psychosis develops in one third of these patientsTay-Sachs Disease (Later Onset Variants)
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)