Genetics- Principles Of Molecular Genetics

Front 1

Thalassemias, Turner Syndrome, retinoblastoma, and PKU are all examples of what type of mutation?

Back 1

Loss of function mutation

Front 2

A mutation that results in an increase in abundance or function is called what?

Back 2

Gain of function mutation

Front 3

What occurs in a "novel property mutation"?

Back 3

change an amino in a protein that results in a mutation.

Front 4

What is an example of a novel property mutation?

Back 4

Sickle cell disease

Front 5

A gene that is expressed at the wrong time or in the wrong place is called a ___

Back 5

Heterochronic or ectopic gene expression

Front 6

Name all the 8 possible steps at which a normal protein can be mutated.

Back 6

- transcription
- translation
- polypeptide folding
-post-translational modification
-assembly of monomers into multimeric proteins
- subcellular localization of polypeptides
- cofactor or prosthetic group binding to polypeptide
- funciton of correctly folded, assembled, adn localized protein produced in normal amounts

Front 7

What are the two classes of hemoglobinopathies?

Back 7

- structural variants
- thalassemias

Front 8

What type of hemoglobinopathy alters the globin polypeptide without affecting the rate of synthesis?

Back 8

Structural variant

Front 9

Most structural variant hemoglobinopathies are caused by what?

Back 9

Point mutations

Front 10

What are the three classes of hemoglobin structural variants?

Back 10

- hemolytic anemias
- hemoglobin with altered oxygen transport
- and a mutation that causes a specific type of thalassemia

Front 11

What gene is mutated in sickle-cell anemia?

Back 11

codon of 6th amino acid of B-globin

Front 12

If a person is homozygous for sickle-cell mutation they will present with what?

Back 12

Sickle cell disease.

Front 13

Sickle cell trait results from what?

Back 13

Heterozygous for sickle cell mutation.

Front 14

When iron in a heme group is oxidized, it creates what?

Back 14

A methemoglobin

Front 15

A methemoglobin is no longer capable of ___

Back 15

Reversible oxygenation

Front 16

What is the function of methemoglobin reductase?

Back 16

Reduction of oxidized hemoglobin back to reduced state ( allows for hemoglobin to pick up another oxygen)

Front 17

Hemoglobins with altered oxygen affinity demonstrate the importance of what?

Back 17

Subunit interaction

Front 18

What is Hemoglobin Kempsey?

Back 18

Prevents oxygen related conformational changes to hemoglobin chains (Hb gets locked into high oxygen affinity and causes polycythemia - can't offload oxygen)

Front 19

Decreased synthesis of one or more globin chains resulting in imbalance of a/B forms is called ____

Back 19

Thalassemia

Front 20

in alpha thalassemia, which chain is messed up?

Back 20

Alpha (B chains normal)

Front 21

In beta thalassemia, which chain is normal?

Back 21

The alpha chain is normal (B chain messed up)

Front 22

What is the single most common single gene mutation in humans?

Back 22

Thalassemias

Front 23

What occurs in Hb Hyde Park?

Back 23

Can't reduce hemoglobin to unoxygenized state. Homozygous = fatal
Heterozygous = cyanotic

Front 24

In thalassemia, the chain produced at normal rate is ___, while the affected chain is ____

Back 24

1. normal = in excess
2. affected = in deficit

Front 25

In thalassemia, excess chains precipitate causing damage to ____, as well as what two problems?

Back 25

1. damage to plasma membrane
2. premature RBC destruction
3. hypochromic, microcytic anemia

Front 26

Why does the body become polycythemic in Hb Kempsey?

Back 26

Body sees that oxygen isn't being released, so they think they have to make more!

Front 27

both fetal and adult hemoglobin is affected by ____ thalassemia

Back 27

Alpha

Front 28

In alpha thalassemia, beta chains begin to form ____ hemoglobin

Back 28

Homotetrameric

Front 29

Homotetrameric hemoglobin is a poor oxygen carrier because ___

Back 29

it can't release oxygen to the tissues.

Front 30

Severe alpha-thalassemias result in ____, mild forms result in ____.

Back 30

1. intrauterine hypoxia = hydrox fatalis
2. anemia = mild

Front 31

What is hydrox fatalis?

Back 31

oxygen cannot be offloaded by hemoglobin and becomes hypoxic resulting in fetal compromise

Front 32

Deletion of a-globin genes are commonly resulting from what?

Back 32

Unequal crossing over

Front 33

What are the three major causes of alpha-thalassemias?

Back 33

- deletion of alpha-globin genes
- ZF deletion
- ATR-X syndrome

Front 34

What is the most common way A-thalassemia occurs?

Back 34

A-globin gene being deleted

Front 35

____ silences the alpha2-globin gene, resulting in a-thalassemia.

Back 35

ZF deletion

Front 36

What is ATR-X syndrome?

Back 36

Thalassemia and mental retardation caused by an X-linked mutation of the ATRX gene.

Front 37

What type of thalassemia results in decreased B-globin production?

Back 37

B- thalassemia

Front 38

Thalassemia beginning postnatal, with hypochromic, microcytic anemia is ___

Back 38

B- thalassemia

Front 39

B-thalassemias are usually due to _____

Back 39

single bp substitutions

Front 40

If a person has mutations of one each alpha and beta globin chains, what would you expect?

Back 40

They cancel each other out & result in fewer symptoms and more normal cells.

Front 41

Thalassemia major results in what?

Back 41

severe anemia

Front 42

thalassemia minor results in ____

Back 42

Slight anemia

Front 43

B-thalassemias can sometimes be caused by defective mRNA synthesis due to ___

Back 43

Errors in splicing, promoter, cap, polyA tail

Front 44

Nonsense and frameshift mutations can result in B-thalassemias by causing ___

Back 44

non-functional mRNA

Front 45

Two copies of the B- thalassemia allele result in ____

Back 45

Thalassemia major

Front 46

Thalassemia minor results from what?

Back 46

Carrying 1 (heterozygous) B-thalassemia mutation)

Front 47

What is the function of housekeeping genes?

Back 47

maintenance of cell structure and function in almost all cells

Front 48

Genes that create unique cellular function in SOME sell types are called what?

Back 48

Specialty genes

Front 49

Mutation in a tissue-specific protein most often results in ___

Back 49

disease restricted to that tissue.

Front 50

____ gene disorders are rarely found in every tissue.

Back 50

Housekeeping

Front 51

A variation in phenotype could be due to one of three types of ___

Back 51

genetic variation.

Front 52

What are the three types of genetic variation?

Back 52

allelic heterogeneity, locus heterogeneity, or effects of modifier genes

Front 53

What is allelic heterogeneity?

Back 53

multiple alleles are at one locus.

Front 54

What is locus heterogeneity?

Back 54

There may be more than one locus for a condition

Front 55

What is genetic variation by effects on modifier genes?

Back 55

Mutations of genes modify expression of another. Result in variations in presentation of a disease (mild to severe)

Front 56

What are three major diseases involving enzymes?

Back 56

aminoacidopathies
lysosomal storage diseasse
altered protein function

Front 57

What is the best example of an aminoacidopathy?

Back 57

hyperphenylalaninemias

Front 58

An increase in blood levels of phenylalanine is called ___ and is an example of a ____

Back 58

1. hyperphenylalaninemias
2. aminoacidopathy

Front 59

All abnormalities resulting in aminoacidopathies are due to loss of function in _____ gene or ____

Back 59

PAH gene, or genes required for proper cofactor (BH4)

Front 60

Phenylketonuria is a classic example of what?

Back 60

inborn error of metabolism

Front 61

An autosomal recessive allele with mutation in the PAH gene is called _

Back 61

Phenylketonuria

Front 62

What does accumulation of phenylalanine resultin in?

Back 62

Damage to CNS

Front 63

Lysosomal storage diseases result in genetic defects in ___

Back 63

lysosomal hydroxylase enzymes

Front 64

Most diseases of lysosomal sorage are a ____ mutation

Back 64

autosomal recessive

Front 65

What does lysosomal storeage diseases cause?

Back 65

accumulation of substrates, unrelenting progression, increased mass of affected tissue/ organ, neurodegeneration

Front 66

What is Tay-Sachs disease?

Back 66

Multiple problems through the body resulting from inability to degrade sphigolipide and therefore decreased hex A

Front 67

___ is a HexA specific deficiency

Back 67

Tay-Sach's disease

Front 68

What are glycosaminoglycans? where are they normally found?

Back 68

polysaccharide chains found in connective tissue.

Front 69

Hunter syndrome has what type of inheritance pattern?

Back 69

X-linked recessive

Front 70

Hurler syndrome has what type of inheritance pattern?

Back 70

autosomal recessive

Front 71

Both Hunter syndrome and Hurler syndrome result in what symptoms?

Back 71

mental retardation, skeletal abnormalities, short stature.

Front 72

What is I Cell disease?

Back 72

loss of glycosylation, protens normally tagged to direct in a cell.

Front 73

Icell disease has what inheritance pattern?

Back 73

autosomal recessive

Front 74

In ____, lysosomal enzymes accumulate in body fluids instead of cells, results in facial feature changes, skeletal changes, growth and mental retardation. (lysosomes eat away at the wrong places)

Back 74

I-cell disease

Front 75

Patients with I-Cell disease have what average life span

Back 75

5-7 yrs

Front 76

What occurs in gains of glycosylation?

Back 76

High proportion of missense mutations create new glycosylation sites.

Front 77

What is MSMD?

Back 77

Mendelian Susceptibility to Mycobacterial Disease - multiple genetic defects that eliminatethe body's ability to fight infection.

Front 78

A cystathionine synthase deficiency that results in impaired cofactor binding is ___

Back 78

Homocystinuria

Front 79

Homocystinuria has what inheritance pattern?

Back 79

autosomal recesive

Front 80

The symptoms in homocystinuria are due to what?

Back 80

build up of homocysteine

Front 81

Familial hypercholesterolemia results from what?

Back 81

mutations in LDL receptor or 3 other possible genes.

Front 82

LDL receptor mutations most commonly result in what?

Back 82

premature heart disease,

Front 83

What transmission pattern occurs in familial hypercholesterolemia

Back 83

autosomal semi-dominant

Front 84

What is the most common fatal autosomal recessive disorder in white children?

Back 84

Cystic fibrosis

Front 85

Cystic fibrosis is a mutation of what gene?

Back 85

CF gene - CFTR

Front 86

In cystic fibrosis, what organs are affected?

Back 86

Lungs and exocrine cells of pancreas

Front 87

In cystic fibrosis, pancreatic defect leads to ___

Back 87

mal-digestion syndrome

Front 88

____ is a severe, untreatable, relatively common X-linked recessive disease.

Back 88

Duchenne muscular dystrophy

Front 89

In Duchenne muscular dystrophy, the gene that codes for ___ is mutated.

Back 89

Dystrophen

Front 90

Duchenne Muscular Dystrophy results in boys who are affected to be normal for ____ and then unlikely to live past ___

Back 90

ok until 1-2 years
dead by 20

Front 91

A type of mutation in the dystrophin gene milder than DMD is called ___

Back 91

Becker Muscular Dystrophy

Front 92

Becker muscular dystrophy is less severe why?

Back 92

Some dystrophin is produced due to the mutated alleles having the proper reading frame.

Front 93

A group of disorders that results in easily fractured bones and skeletal deformities with a wide clinical range is ___

Back 93

osteogenesis imperfecta

Front 94

How many major phenotypes are there of osteogenesis imperfecta?

Back 94

4

Front 95

This disease usually manifests ages 60-90, but monogenic forms may present earlier.

Back 95

Alzheimer's

Front 96

Alzheimers results in what presentation?

Back 96

progressive deterioration of memory and higher cogntiive functions, behavioral changes