Exam V: Genetics I

Question 1

SNP

Answer 1

Most common is the SNP (single nucleotide polymorphism)
A single nucleotide where two different bases are common
AAGTCAC or AAGCCAC
May be in any part of the genome
Coding sequence, intron, promoter, UTR, intergenic regions
Useful in gene mapping studies

Question 2

Point Mutation

Answer 2

Single base change
Three types when in coding regions
Silent - no change in protein sequence
Missense - change one amino acid to another
Nonsense - makes STOP codon

Question 3

Insertion/Deletion

Answer 3

Change number of bases
May be one or more bases
Can be very large number
Will disrupt reading frame if not a multiple of 3
Frameshift mutations

Question 4

X Linked Disorders

Answer 4

Hemophilia A
Duchenne’s muscular dystrophy
Red-green color blindness

Question 5

Marfan Syndrome

Answer 5

Mutation in fibrillin-1 (FBN1) gene
Important in skeleton, eye, blood vessels
Generally autosomal dominant
New mutations are common in sporadic cases
Long limbs, arachnodactyly, lens displacement
Blood vessel defects can be dangerous, dilation of ascending aorta, may rupture

Question 6

Ehlers Danlos Syndrome

Answer 6

Series of disorders affecting collagen
Some autosomal dominant, collagens
Some autosomal recessive, processing enzymes (lysyl hydroxylase, peptidase)
Affects skin, ligaments and joints mainly
Skin hyperextensible, joints hypermobile
Internal problems – colon or large artery rupture, diaphragmatic hernia

Question 7

Alkaptonuria

Answer 7

First “inborn error of metabolism” defined
Inability to metabolize tyrosine properly
Published by Garrod in 1902
Defect in homogentisate oxidase
Homogentisic acid accumulates, excreted in urine
Will turn black upon oxidation
Deposits in joint cartilage, becomes brittle

Question 8

LDL Receptor

Answer 8

Protein made in hepatocytes
Modified in ER and Golgi, go to membrane
Bind LDL in coated pits
Endocytosed in endosomes
LDL to lysosomes for degradation
LDLR back to surface

Any extra TG are taken up by liver, but the LDL receptor is defective and you have LDL circulating

Question 9

Familial Hypercholesterolemia

Answer 9

Mutations in LDLR gene
Autosomal Dominant, double the normal serum cholesterol
Increased risk of coronary artery disease
Xanthomas form
Many types of mutation

Question 10

Lysosomal Storage Disorders and Degradation

Answer 10

Lysosomes degrade many materials
Specific enzymes targeted to lysosomes
Mannose-6-phosphate added as tag
Go to lysosome instead of being secreted

Degrade complex and unusual molecules
Glycosaminoglycans, sphingolipids, etc.
Done in step-wise fashion
If cannot perform a step, remaining material accumulates

Question 11

GM2 Ganglioside Degradation

Answer 11

Sphingolipid found in nervous system
Three genes for three polypeptides necessary for normal function
Defect in α subunit leads to Tay-Sachs
Defect in ß subunit leads to Sandhoff disease

Question 12

Tay Sach’s Pathology

Answer 12

Sphingolipid accumulates in various tissues
Causes lysosomes to balloon to large size
Major problem is in neurons of the CNS

Question 13

Niemann Pick Disease

Answer 13

NP A and B are sphingomyelinase deficiencies
Accumulates in nervous tissue and many organs
Many small vesicles cause foamy appearance
NPC is defect in cholesterol trafficking

Question 14

Gaucher Disease

Answer 14

Defect in glucocerebrosidase
Most common of all lysosomal storage disorders
Mainly affect phagocytes, can have neural involvement in severe cases

Gaucher cells are plump macrophages that characteristically have the appearance in the cytoplasm of crumpled tissue paper due to accumulation of glucocerebroside.
Mainly affects bone marrow - Erlenmeyer Flask Deformity
Find fat in bone marrow
Crumpled tissue paper looking Gaucher cell

Question 15

Mucopolysaccharidoses

Answer 15

Defects in enzymes that degrade GAGs
Complex carbohydrate chains with many unusual components (e.g., iduronic acid)
Hunter – X-linked recessive- MPS II
Hurler – autosomal recessive- MPS I
Defects in specific enzymes
Coarse facies, skeletal dysplasia, growth retardation, multiple organ involvement

Question 16

Glycogen Metabolism

Answer 16

Glycogen is storage carbohydrate
Can be converted to glucose when needed
Most stored in liver, some in muscle and kidney
Differences in metabolism between tissues

Question 17

Hepatic vs. Muscular

Answer 17

Liver stores glycogen to provide glucose to other tissues
Degrade glycogen, then export glucose
Muscle cannot export glucose, uses it for generating energy
Disorders can differ

Question 18

von Gierke Disease

Answer 18

Lack of glucose-6-phosphatase
Cannot export glucose from glycogenolysis
Hepatomegaly and renomegaly with large glycogen deposits, some fat deposition
Hypoglycemia, may lead to convulsions
Hyperlipidemia, hyperuricemia, xanthomas
Failure to thrive, stunted growth

Question 19

McArdle Disease

Answer 19

Defect in muscle glycogen phosphorylase
Glycogen accumulates in striated muscle
Muscles cramp with exercise
Myoglobin and creatine kinase released
Lactate levels do not increase with exercise
Onset usually in adulthood

Question 20

Pompe Disease

Answer 20

Defect in acid maltase
Liver, skeletal muscle and heart have glycogen deposits, some ballooning
Different levels of effect, serious causes massive cardiomegaly, muscle hypotonia, cardiorespiratory failure in first years of life
Later onset form mainly causes muscle hypotonia, progressive
Glycogen appears clear in Pompe muscle fibers

Question 21

CF Pathology

Answer 21

Infects the pancreas and lungs mainly- see fibrosis, cysts, dilated ducts full of secretions/clogged, inspissated secretions (thickened/dried), preserved islets, lung airways with pus with acute inflammatory cells and clogged aveoli
All because they lack body secretions