Week 5- Molecular Disease Flashcards by Meg Dolohanty

What are the four effects of mutation on protein function ?

Loss of function mutation
Gain of function mutation
Novel property mutation
Heterochronic or ectopic gene expression

How well did you know this?

Not at all

Perfectly

What are four disorders associated w/ loss of function?

Thalassemias
Turner syndrome
retinoblastoma
PKU

How well did you know this?

Not at all

Perfectly

What do novel property mutations result in?

Change aa in protein due to mutation

How well did you know this?

Not at all

Perfectly

What is an example of a novel property mutation?

Sickle cell disease

How well did you know this?

Not at all

Perfectly

What are heterochronic or ectopic gene expression due to?

Genes expressed at wrong time or in wrong place

How well did you know this?

Not at all

Perfectly

When do alpha hemaglobinopathies affect individuals?

as a fetus and adult

How well did you know this?

Not at all

Perfectly

When do beta hemoglobinopathies affect individuals?

Post natal life

How well did you know this?

Not at all

Perfectly

what are the two types of hemoglobinopathies

Structural variants

Thalassemias

How well did you know this?

Not at all

Perfectly

what causes sickle-cell anemia?

Single nucleotide substitution
Changes of codon of 6th aa of Beta-globin
glutamic acid turns into a valine

How well did you know this?

Not at all

Perfectly

If you are homozygous for the sickle-cell anemia trait what do you have?

Sickle cell disease

How well did you know this?

Not at all

Perfectly

Who carries the sickle cell trait?

Individuals heterozygous for the sickle-cell trait

How well did you know this?

Not at all

Perfectly

When Fe in heme group is oxidized, what happens?

Methemoglobin is created- can’t do reversible oxygenation

How well did you know this?

Not at all

Perfectly

What does methemoglobin reductase do?

Reduces Fe

How well did you know this?

Not at all

Perfectly

What happens in Hb Hyde Park?

Individual is resistant to methemoglobin reductase

Individuals becomes cyanotic

How well did you know this?

Not at all

Perfectly

What happens with Hb Kempsey?

Hb locked into high O2 affinity- causes polycythemia because not enough oxygen is getting to the tissues so body produces more RBC

How well did you know this?

Not at all

Perfectly

What type anemia do thalassemias lead to?

Hypochromic, microcytic anemia

How well did you know this?

Not at all

Perfectly

in alpha thalassemias, what do beta chains form?

Homotetrameric hemoglobin- inefffective O2 carrier

How well did you know this?

Not at all

Perfectly

In severe forms of alpha thalassemias- what happens?

Intrauterine hypoxia (baby born in congestive heart failure)

How well did you know this?

Not at all

Perfectly

What happens with mild forms of alpha thalassemias?

Anemia

How well did you know this?

Not at all

Perfectly

What is the most common form of alpha thalassemias?

Deletion of alpha-globin genes

due to unequal crossing over (SE Asia)

How well did you know this?

Not at all

Perfectly

What happens in a ZF deletion in alpha thalassemias?

silences the alpha 2 globin gene (alpha 1 destroyed)

How well did you know this?

Not at all

Perfectly

what is ATR-X syndrome?

Thalassemia and mental retardation

How well did you know this?

Not at all

Perfectly

What type of disorder is ATR-X syndrome?

X-linked; mutation of ATRX gene

How well did you know this?

Not at all

Perfectly

What type anemia is there in beta thalassemias?

hypochromic, microcytic anemia

How well did you know this?

Not at all

Perfectly

What is beta thalassemia usually due to?

Single bp substitution

What usually creates alpha thalassemia?

Deletion

What type of thalassemia have a very large number of allele forms?

Beta

What causes thalassemia major?

two thalassemia alleles

What causes thalassemia minor?

1 Beta thalassemia allele | Have slight anemia

If a person has thalassemia major- are their alleles for the disorder likely identical or different?

Different

What can cause defective mRNA synthesis in Beta thalassemias?

splicing, promoter, cap, poly A tail

What can produce non-functional mRNAs in beta thalassemias?

nonsense and frameshift mutations

Where are housekeeping genes found?

Virtually all cells

What do housekeeping genes do?

Maintenance of cell structure and function

If you have a mutation in a housekeeping gene- where are the disorders found?

In the same tissue

What is Allelic heterogeneity ?

Multiple alles at a locus | alleles that confer residual function create milder form of disease

What is Locus heterogeneity ?

more than 1 locus for a condition

What are two disorders that have modifier genes?

Thalassemia and cystic fibrosis

What is the best example of an aminoacidopathy?

hyperphenylalaninemias

What are abnormalities in hyperphenylaninemias due to?

Loss of function in PAH gene or genes required for proper cofactor (BH4)

What can't you turn phenylalanine into in hyperphenylalaninemias?

tyrosine

What type of disorder is phenylketonuria?

Autosomal recessive- mutations in PAH

in lysosomal storage diseases- what is the a genetic defect in?

lysosomal hydroxylase enzymes

What do all lysosomal storage diseases have in common?

Substrates accumulate | unrelenting progression

What happens to the brain in lysosomal storage diseases?

Neurodegenerative disorder

What type of mutations are lysosomal storage diseases?

Autosomal recessive

In Tay-Sachs a deficiency in ______ leads to an accumulation of ________

a deficiency of hexosamidiase A (hex A) leads to Sphingolipid (ganglioside) accumulation

How many enzymes create hex A?

3 enzymes

Tay Sachs is a ____ deficiency.

HEXA

what are two types of Mucopolysaccharidoses?

Hunter syndrome | Hurler syndrome

What is the inheritance pattern of Hunter syndrome?

X-linked recessive

What is the inheritance pattern of Hurler syndrome?

Autosomal recessive

What symptoms are found in both hunter and hurler?

mental retardation, skeletal abnormalities, short stature

What is I cell disease due to?

Loss of glycosylation (enzymes are properly directed to lysosomes but are out in body)

What has an individual gained in MSMD (Mendelian susceptibility to mycobacterial disease )

glycosylation

What is homocystinuria due to?

Inability to effectively break down homocysteine

What is there a deficiency of in homocystinuria?

Cystathionine synthase - impaired cofactor binding

What causes familial hypercholesterolemia?

Mutations in LDL receptor or 3 other genes

What transmission pattern does familial hypercholesterolemia have?

Autosomal trait- semi dominant, has dosage effect

What is affected in cystic fibrosis?

Lungs and exocrine pancreas (thick secretions)

What is the cystic fibrosis gene?

CFTR

Why can't individuals with cystic fribrosis digest foods?

Pancreatic defect

What population does duchenne muscular dystrophy affect?

boys normal for 1-2 years, unlikely to live past 20

In MSMD (Mendelian susceptibility to mycobacterial disease), and individual has multiple genetic defects that eliminate the bodies ability fo fight what?

Infection

What is the milder form of muscular dystrophy?

Becker, only produce some dystrophin; has proper reading frame

What is a group of disorders where individual easily fracture bones?

Osteogenesis Imperfecta

Where do 90% of mutations in osteogenesis imperfecta occur?

COLIAI COLIA2 Both code for chains in type I collagen

What decades does Alzheimers Disease manifest in?

6th to 9th

Where is there degeneration of neurons in Alzheimers Disease?

Cerebral Cortex and HIppocampus

What Hb disorder causes polycythemia?

Hb Kempsey

What codon does sickle cell disease affect?

Changes of codon of 6th aa of Beta-globin

What disease involves a loss of glycosylation?

I-Cell Disease

What disease involves a gain of glycosylation?

Mendelian Suspectiability to Mycobacterial Disease (MSMD) | Body can't fight infection

In Becker muscular dystrophy, the DNA sequence still have the proper ______ which leads to less destructive effects?

Reading frame