Genetic Diseases

Question 1

How many Chromosomes do humans have?

Answer 1

22 pairs of autosomes
1 pair of sex chromosomes
46 total

Question 2

Alterations in the genetic code are termed what?

Answer 2

Mutations

Question 3

What is it called when one chromosome in the pair is effected?

Answer 3

Heterozygous

Question 4

What is it called when both chromosomes in the pair are effected?

Answer 4

Homozygous

Question 5

Mutations affecting somatic cells

Answer 5

May result in tumors or developmental malformations

Question 6

Mutations affecting germ cells

Answer 6

Can be inherited

Question 7

What are the different types of mutations?

Answer 7

Point mutations
Frameshift
Trinucleotide repeat

Question 8

Point mutations

Answer 8

Single base mutation

Ex: Sickle Cell Anemia

Question 9

Frameshift

Answer 9

There is an insertion or deletion of 1-2 base pairs, which can cause alterations/shifts in reading or early stoppage

Question 10

Trinucleotide repeat

Answer 10

An amplification of a 3-nucleotide sequence

Question 11

What are the different types of polymorphisms?

Answer 11

Single nucleotide polymorphism

Copy Number Variations

Question 12

Single nucleotide polymorphism

Answer 12

Variation in just one nucleotide at at a single site on the DNA molecule
May not cause disease by themselves, but can be precursors for multigene diseases such as diabetes or hypertension

Question 13

Copy number variation

Answer 13

A particular gene that varies from one individual to the next
Different numbers of large continuous stretches of DNA

Question 14

Epigenetic Changes

Answer 14

Modulation of gene expression without altering the DNA sequence
-usually chemical modifications

Methylation of promoter regions make them inaccessible to RNA polymerase - reducing the expression

Question 15

Alterations to Non-coding RNAs

Answer 15

micro-RNAs (mRNA) inhibit translation of their target messenger RNA into their corresponding proteins
-they can come in and silence tumor suppressor elements

Question 16

Diseases caused by Single gene defects

Answer 16

Genetic alterations often results in the production of an abnormal protein, which can alter the phenotype

Question 17

T/F - a mutation has to occur at the same basepair in order to cause the same phenotypic alteration

Answer 17

False - because genes are comprised of many base pairs, a mutation can occur t different places within the gene, yet produce essentially the same phenotypic alteration

Question 18

Autosomal Dominant Disorders

Answer 18

Mutated gene can be on one of the autosomes and the disease will be clinically evident
Delayed onset - even though the mutant gene is present form birth

Question 19

If one parent is a carrier for an Autosomal dominant disorder, what is the likelihood a child will have it?

Answer 19

50%

Question 20

What are the types of autosomal dominant disorders?

Answer 20

Reduced/Incomplete Pentrance
Variable Expressivity
De novo mutation

Question 21

Reduced/Incomplete Penetrance

Answer 21

If a person has a mutant gene, but doesn’t or only partially expresses it phenotypically

Question 22

Variable Expressivity

Answer 22

Expression can be identified in all effected persons, but to different extents

Question 23

De novo mutations

Answer 23

AD disorder where neither parent is affected and there is no family history in the pt

Question 24

Autosomal Recessive Disorder

Answer 24

Trait is expresssed only if both genes at a given loci are mutated
Parents of the affected pt usually don’t show the disease phenotypically
Many are enzyme defects leading to metabolic dysfunciton
Age of onset is early
Complete penetrance is common

Question 25

If both parents are carriers of an AR disorder, what is the liklihood that the kids have the disorder?

Answer 25

25% of having the disorder | 50% of being carriers

Question 26

What are heterozygous carriers of AR disorders unaffected?

Answer 26

They typically have reduced, but still adequate levels of normal functional enzymes

Question 27

X-linked disorders

Answer 27

aka Sex-linked | All the mutations are on the X-chromosome

Question 28

What type of disorder is the most common X-linked disorder?

Answer 28

X-Linked Recessive

Question 29

X-Linked Recessive

Answer 29

Females having 2 X-chromosomes are usually unaffected Heterozygous females are carriers Homozygous females express the disease Hemizygous males express the disease

Question 30

Lyonization

Answer 30

Rarely, heterozygous females may demostrate full expression of X-linked recessive diseases 16 days post-conception, most of (>75%) of one X-chromosomes are inactivated randomly Results in the formation of a Barr body in each cell Either the maternal or paternal X may be inactivated

Question 31

What are some diseases caused by Mutations in structural proteins?

Answer 31

Marfan Syndrome | Ehlers-Danlos Syndrome

Question 32

Marfan Syndrome cause

Answer 32

Autosomal Dominant Mutation of the FBN1 gene The mutation results in abnormal fibrilin; which is important for normal elastic fiber production

Question 33

Marfan Syndrome Symptoms

Answer 33

``` Tall, thin body appearance -abnormally long legs -Arachnodactyly Dislocation of the eye lens Aortic aneurysm leading to heart failure and aortic rupture ```

Question 34

Ehler-Danlos Syndrome

Answer 34

Mutation causes a problem with collagen synthesis

Question 35

Ehler-Danlos Syndrom Symptoms

Answer 35

Hyperextensible skin and hypermobile joints Skin fragility and delayed wound healing Rupture of colon and large arteries Hernia

Question 36

What is the signature disease caused by mutations in genes encoding receptor proteins or channels

Answer 36

Familial Hypercholesterolemia

Question 37

Familial Hypercholesterolemia cause

Answer 37

Autosomal Dominant Mutation in the gene that encodes the LDL receptor - resulting in impaired metabolism and increased LDL cholesterol in the plasma

Question 38

Familial Hypercholesterolemia Symptoms

Answer 38

Multiple Xanthomas (lipid filled lesions) of the skin and premature atherosclerosis

Question 39

Heterozygous Hypercholesterolemia

Answer 39

2-3x more LDL than healthy individuals

Question 40

Homozygous Hypercholesterolemia

Answer 40

>5x more LDL than healthy individuals | Often die via MI by age 20 - early treatment can help, but pts are still high risk

Question 41

Iomitapide

Answer 41

Recently approved drug to help treat Homozygous Hypercholesterolemia

Question 42

What are some diseases caused by Mutations in Enzyme Proteins?

Answer 42

Phenylketonuria | Lysozomal Storage Diseases

Question 43

Phenylketonuria

Answer 43

Autosomal Recessive | Severe lack of phenylalanine hydroxylase leading to hyperphenulalaninemia and PKU

Question 44

Phenylketonuria symptoms

Answer 44

Affects 1:10k caucasian infants Affected infants seem normal at birth, bu elevated phenylalanine levels impair brain development and cause mental retardation by 6 mo

Question 45

Phenylketonyuria treatment

Answer 45

Screening of newborns is mandatory in the US | Restricted dietary sources of phenylalanine will prevent the development of retardation

Question 46

Lysozomal Storage disease

Answer 46

Autosomal recessive Commonly affects infants and youn children Accumulation of insoluble large molecules in macrophages, leading to hepatosplenomegaly -this decreases the cell's efficiency and makes it useless Frequent CNS involvement leads to neuronal damage, mental retardation, and/or early death

Question 47

Mucopolysarccharidoses

Answer 47

Autosomal Recessive Caused by lack of any one of several enzymes necessary to degrade mucopolysaccharides Affected patients have coarse facial features, clouding of cornea, stiff joints, and mental retardation

Question 48

Hurler Disease

Answer 48

Autosomal Recessive Caused by deficiency of alpha-L-iduronidase Life expectancy is 6-10 yrs Bone marrow transplant or enzyme replacement may improve outlook, but not all aspects are corrected

Question 49

Hunter Syndrome

Answer 49

X-Linked Deficiency in L-iduronate sulfatase Absence of corneal clouding and milder clinical course, but very similar to Hurler's

Question 50

What are some examples of things with Multifactorial Inheritance

Answer 50

``` Height Weight BP Hair color Diabetes Hypertension Gout Schizophrenia ```

Question 51

What causes 50% of first trimester spontaneous abortions?

Answer 51

Chromosmal abnormalities

Question 52

What are the different Numeric abnormalities of chromosomes?

Answer 52

Polyploidy | Aneuploidy

Question 53

Euploidy

Answer 53

Normal chromosome count | 46

Question 54

Polyploidy

Answer 54

An increased chromosome count that is a multiple of what is normall seen ie 3x23 = 69 4x23 = 92

Question 55

What is Aneuploidy and what are the different types?

Answer 55

Any number that is not an exact multiple of the normal count Trisomy Monosomy

Question 56

Trisomy

Answer 56

Extra chromosome

Question 57

Monosomy

Answer 57

Missing a chromosome

Question 58

What are the different Structural Autosomal Abnormalities?

Answer 58

Translocation Deletion Inversion

Question 59

What causes Structural Autosomal Abnormalities?

Answer 59

Results from chromosome breakage followed by loss or rearrangement of material

Question 60

Translocation Autosome abnormality

Answer 60

Transfer of a part of one chromosome to another nonhomologous chromosome (a different chromosome) -known as reciprocal translocation

Question 61

Deletion Autosomal abnormality

Answer 61

Loss of a portion of a chromosome

Question 62

Inversion Autosomal abnormality

Answer 62

Chromosome breaks in two, and the released fragment flips and is reunited

Question 63

Trisomy 21

Answer 63

Downs Syndrome Due to meiotic non-disjunction of chromosome 21 during ovum formaiton More likely in older mothers

Question 64

Trisomy 21 Symptoms

Answer 64

``` Mental retardation Epicanthic folds Flat facial profile Cardiac malformations Increased susceptibility to infections Large tongue Increased risk of acute leukemia ```

Question 65

Jimmy Kleinfelter syndrome

Answer 65

Male hypogonadism where there are at least 2 X chromosomes and one or more Y chromosomes Most common form is XXY Pts are phenotypically male

Question 66

Kleinfelter syndrom Symptoms

Answer 66

``` Increased length of lower limbs Reduced body hair Gynecomastia Hypogonadism Most common form of male sterility Increased frequency of taurodontism ```

Question 67

Turner Syndrome

Answer 67

Partial or complete abscence of one of the X chromosomes (45 total chromosomes)

Question 68

Turner Syndrome Symptoms

Answer 68

``` Short stature Webbing of neck Low posterior hairline Shield-like chest High-arched palate Variety of congenital cardiovascular malformations Failure to develop secondary sex characteristics Amenorrhea (absence of menstruation) ```

Question 69

Prenatal indications for genetic analysis

Answer 69

Mother's age >34 yrs Parent is a carrier of a chromosomal translocation or X-linked disorder Hx of previous child with chromosome abnormality

Question 70

Postnatal indications for genetic analysis

Answer 70

``` Mutiple congenital abnormalities Unexplained reatardation Suspected aneuploidy Suspected sec chromosomal abnormality Infertility Multiple spontaneous abortions ```