Genetics

Question 1

Each gene contains the genetic information required to produce a _____. Each of these is made specifically to perform a necessary body function

Answer 1

protein

Question 2

Mutation of a gene locus affecting only one chromosome? Both chromosomes?

Answer 2

heterozygous for the disorder

homozygous for the disorder

Question 3

Permanent change in DNA

Answer 3

mutation

Question 4

Mutation affecting germ cells can….

Answer 4

be transmitted to progeny aka is inherited

Question 5

Mutations affecting somatic cells can…

Answer 5

form tumors or developmental malformations

Question 6

3 types of mutations

Answer 6

point mutation (missense mutation)
frameshift mutation
Trinucleotide repeat mutations

Question 7

Describe Point mutations and give example

Answer 7

single nucleotide base substitued

i.e sickle cell anemia

Question 8

Describe frameshift mutation

Answer 8

when one or two base pairs are inserted or deleted causing an alteration in the reading frame of the DNA strand

Question 9

Describe trinucleotide repeat mutation and give an example

Answer 9

Amplification of sequence of 3 nucleotides

i,e- Fragile X syndrome - a normal human has 5-54 repeats of CGG, while a person with Fragile X syndrome has 230-4000

Question 10

3 examples of alterations in protein-coding genes other than mutations

Answer 10

1. Polymorphisms - single nucleotide polymorphism and copy number variations
2. Epigenetic changes
3. Alterations in non-coding RNAs

Question 11

Describe single nucleotide polymorphism and give examples of what this could be a marker of:

Answer 11

variation in just one nucleotide at a single site on the DNA molecule.

May be markers for diabetes or hypertension

Question 12

What is the difference between single nucleotide polymorphism and point mutation

Answer 12

the frequency.

Missense/point mutations dont occur often
Single nucleotide polymorphism occurs VERY ofter

Question 13

How many single nucleotide polymorphisms have been identified and where do most occur

Answer 13

Over 6,000,000 have been identified, but most are within exons, introns, or intergenic regions

Question 14

Describe copy number variations and what does this account for….

Answer 14

When you have different numbers of large continuous stretches of DNA, from 1,000 to millions of base pairs.

This may account for phenotypic variation

Question 15

What is an epigenetic change?

Answer 15

when a modulation of gene expression occurs without an altered DNA sequence

ie. a methylation of promoter regions makes them inaccessible to RNA polymerase causing reduction in protein synthesis

Question 16

Describe alterations in non-coding RNAs

Answer 16

micro-RNAs inhibit translation of their target messenger RNAs into their corresponding proteins

Question 17

T or F; Autosomal dominant disorders create outward physical changes and many exhibit a delayed age of onset even though the mutant gene has been there since birth

Answer 17

true

Question 18

2 examples of autosomal dominant disorders

Answer 18

Huntington disease
Neurofibromatosis (from lecture) - seen nearly 100% of the time but the extent is variable - some people have tumors everywhere on their body

Question 19

Define reduced or incomplete penetrance

Answer 19

person has a mutant gene but does not express it phenotypically

Question 20

define variable expressitivity and what autosomal dominant disorder is an example of this

Answer 20

trait is seen phenotypically in the individuals having the mutant gene but is expressed differently among individuals

Question 21

Define: de novo mutation

Answer 21

affected individuals may not have affected parents because their disease arose from a new mutation

Question 22

What represents the largest group of mendelian disorders?

Answer 22

autosomal recessive

Question 23

In autosomal recessive disorders, if the mutant gene is rare, there is a strong probability that the affected child (proband) is the product of a _________________

Answer 23

consanguineous relationship (coming from the same descendants)

Question 24

In autosomal recessive disorders, the age of onset is more frequent at what period in life?

and

describe the expression of the defect

Answer 24

early in life

and

defect tends to be more uniform and complete penetrance is common

Question 25

What is the one Y-linked disorder?

Answer 25

hairy ears

Question 26

Almost all x-linked disorders are: recessive or dominant?

Answer 26

recessive

Question 27

Who is affected by x-linked disorders?

Answer 27

females who are homozygous for the disorder (unless they have an unusual x-linked dominant disorder) and all males because they only have one x-chromosome

Question 28

what would be the reason a heterozygous woman may demonstrate full expression even though the x-linked disorder is recessive?

Answer 28

unfavorable lyonization (inactivation of an abnormally high percentage of normal X chromosomes leading to clinically evident heterozygote disease)

Question 29

Describe lyonization

Answer 29

- occurs only in females - 16 days after conception, all but one X chromosome is randomly inactivacted in all of the cells of the zygote - either the maternal or paternal X may be inactivated in each cell and that X remains inactivated for life

Question 30

Example of X-linked dominant

Answer 30

Oral-Facial-Digital syndrome (OFD) type I

Question 31

Diseases caused by mutations in STUCTURAL PROTEINS

Answer 31

Marfan syndrome | Ehlers-Danlos Syndromes

Question 32

How does Marfan Syndrome: - occur - give general characteristics of people who tend to get this - prevalence - symptoms people with syndrome get

Answer 32

Autosomal dominant disorder of CT due to mutation of "FBN1 gene" --> you get abnormal "fibrillin" (which is a glycoprotein necessary for normal elastic fiber production 1 in 5000 Tall, thin body with abnormally long legs, arms, and fingers (Wolters....) Dislocation of the eyes Aortic aneurysm and dissection leading to heart failure and aortic rupture

Question 33

How does Ehlers-Danlos syndrome come about? Symptoms of people who get it?

Answer 33

collagen synthesis problem - hyperextensible skin and hypermobile joints (can extend fingers all the way back) - Skin fragility and delayed wound healing - rupture of colon, large arteries - hernias

Question 34

Diseases caused by mutations in RECEPTOR POINTS

Answer 34

``` Familial Hypercholesterolemia Cystic Fibrosis (lecture) ```

Question 35

Frequency of hypercholesterolemia? Where is the mutation? What can this cause?

Answer 35

One of the most common inherited disorders: 1 in 500 Mutation in the gene for the LDL receptor resulting in impaired metabolism and increased LDL cholesterol in plasma This causes: xanthomas of the skin premature atherosclerosis - plaque build-up in arteries

Question 36

In hypercholesterolemia, how much more cholesterol do homozygotes and heterozygotes have compared to the normal levels?

Answer 36

homozygous - 5X -often die of MI before age of 20 heterozygous - 2-3X

Question 37

In hypercholesterolemia, understanding the role of LDL receptors have led to the design of what medication? And what does this medication control?

Answer 37

the statin family of drugs | -they control cholesterol levels

Question 38

Diseases caused by mutations in ENZYME PROTEINS

Answer 38

Phenylketonuria and ``` Lysosomal Storage Diseases Tay-Sachs disease Niemann-Pick disease Gaucher disease Mucopolysaccharidoses ```

Question 39

Phenylketonuria: - Type of disorder: dominant or recessive? - prevalence and whose affected? - lack of what enzyme? and what does this lead to? - when does onset occur? - how can this be treated if detected early on?

Answer 39

- autosomal recessive disorder - 1 in 10,000 white infants - lack of phenylalanine hydroxylase, leading to hyperphenylalaininemia and PKU - normal at birth, but within 6 months elevated phenylalanine levels impair brain development and mental retardation is evident - Screening at birth is mandatory in USA and restricting dietary phenylalanine intake will prevent mental retardation

Question 40

Lysosomal Storage Diseases - Type of disorder: dominant or recessive? - Whose affected? - How does this occur? - Symptoms of a person withthis?

Answer 40

- Autosomal recessive transmission - infants and young children - accumulation of insoluble large molecules in macrophanges with hepatosplenomegaly - frequent CNS involvement, mental retardation, and/or early death

Question 41

what is it called if two or more genes, plus environmental/nongenetic influences, are responsible for a disorder? give an example

Answer 41

multifactorial inheritance ie- genes make one susceptible for diabetes and obesity is the environmental factor contributing as well

Question 42

What is the composite picture of the human chromosome strands that are stained, photographed, and arranged in pairs?

Answer 42

karyotype

Question 43

In as many as 50% of 1st trimester spontaneous abortions, the fetus has a ________

Answer 43

chromosomal abnormality

Question 44

Euploid is

Answer 44

a normal chromosomal count (2 x 23 = 46)

Question 45

Polyploidy is

Answer 45

an increased chromosomal count that is a multiple of that normally seen (3 x 23 or 4 x 23) results in spontaneous abortion

Question 46

Aneuploidy and examples of it

Answer 46

any number that is not an exact multiple of the normal chromosome count examples include: an extra chromosome (trisomy = 2 X 23 + 1 = 47) an absence of a chromosome (monosomy 2 X 23 -1 = 45)

Question 47

Translocation is...

Answer 47

the transfer of a part of one chromosome to another nonhomologous chromosome

Question 48

Trisomy 21 aka Down Syndrome: - Is it common within chromosomal disorders? - What is associated with this occuring? - Symptoms of child with this syndrome?

Answer 48

-Most common of the chromosomal disorders -associated with increased maternal age 45 years old - 1:25 -mental retardation, epicanthic folds (skinfold of upper eyelid covering inner angle of eye), flat facial profile, increased susceptibility to infection (severe periodontal disease in childhood), large tongue, cardiac malformations

Question 49

-How does Trisomy 21 occur?

Answer 49

-this occurs due to meiotic non-disjunction of chromosome 21 during formation of the ovum

Question 50

Klinefelter Syndrome: - What is the mutation - Characteristics/symptoms - Dental fact

Answer 50

defined as male hypogonadism that develops when there are two X chromosomes and one or more Y chromosomes - increased length of lower limbs, reduced body hair, gynecomastia - most common reason for hypogonadism (swelling of breasts in males) - increased frequency of taurodontism (body of tooth and pulp chamber is enlarged vertically at the expense of the roots)

Question 51

Turner Syndrome - What is the mutation - Symptoms of people with this

Answer 51

due to partial or complete absence of the X chromosomes -short stature, webbed neck, low post hairline, high-arched palate. primary amenorrhea (absence of menstruation)

Question 52

Diagnosis of Genetic diseases

Answer 52

1. fluorescence in situ hybridization 2. comparative genomic hybridization 3. molecular diagnosis of genetic disorders

Question 53

How is fluorescence in situ hybridization achieved?

Answer 53

used fliorescent dye-labeled probes that recognize sequences specific to chromosomal regions

Question 54

How is comparative genomic hybridization achieved?

Answer 54

uses different colored dyes attached to large segments of the test DNA and normal DNA, followed by hybridization

Question 55

How is molecular diagnosis of genetic disorders achieved?

Answer 55

1. PCR analysis - amplify the DNA in question 2. compare the order of nucleotides of this DNA to a normal DNA sequence 3. use restriction enzymes and run the segments on gel electrophoresis, compare to normal DNA

Question 56

Prenatal Indications for genetic analysis

Answer 56

- mother's age > 34 years - parent who is a carrier of a chromosomal translocation - history of a previous child with chromosomal abnormality - parent who is a carrier of an x-linked disorder

Question 57

Postnatal indication for genetic analysis

Answer 57

- multiple congenital abnormalities - unexplained mental retardation and/or delayed development - suspected aneuploidy (ie - down syndrome) - suspected sex chromosomal abnormality - infertility - multiple spontaneous abortions