Genetics

Question 1

what happens to the mutations affecting germ cells?

Answer 1

can be transmitted to progeny

Question 2

what happens to the mutations affecting somatic cells?

Answer 2

result in tumors or developmental malformations

Question 3

what is a point mutation? example?

Answer 3

single nucleotide base substituted

sickle cell anemia

Question 4

what is frameshift mutation

Answer 4

insertion or deletion of one or two base pairs, altering reading frame of the DNA strand

Question 5

what is trinucleotide repeat mutations?

examples?

Answer 5

amplification of sequence of 3 nucleotides

fragile X syndrome

Question 6

what is a single nucleotide polymorphism?
how many have been identified?
what is the significance of them?

Answer 6

variation in just one nucleotide at a single site on the DNA molecule
over 6 million have been identified but most are within exons, introns or intergenic regions
they may be markers for multigenic complex diseases, such as diabetes or hypertension

Question 7

what are copy number variations?

Answer 7

different numbers of large contiguous stretches of DNA, from 1000 to millions of base pairs
about half involve gene coding sequences, and this may account for much phenotypic variation

Question 8

what are epigenetic changes?

Answer 8

modulation of gene expression without altered DNA sequence
important in development and normal homeostasis.
methylation of promoter regions make them inaccessible to RNA polymerase, thus reducing protein synthesis

Question 9

alterations in non-coding rnas

Answer 9

micro RNAs (miRNA) inhibit translation of their target messenger RNAs into their corresponding proteins

Question 10

what are the types of genetic disorders?

Answer 10

disorders with multifactorial (polygenic) inheritance

cytogenetic disorders- chromosomal aberrations (autosomes and sex chromosomes)

Question 11

what are autosomal dominant disorders?

Answer 11

altered gene locus is on an autosome and the disease will be evident clinically when only one of the chromosomes in the pair exhibits a mutation at the affected gene locus

Question 12

characteristic of autosomal dominant disorders

Answer 12

majority of disorders create outward physical changes and many exhibit a delayed age of onset, even tho the mutant gene is present from birth
one of the parents is usually affected, and both males and females can have the disorder and transmit the mutant gene

Question 13

what is reduced or incomplete penetrance?

Answer 13

person has a mutant gene but does not express it phenotypically

Question 14

what is variable expressivity?

Answer 14

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

Question 15

what is de novo mutation?

Answer 15

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

Question 16

what is neurofibromatosis?

Answer 16

example of nearly 100% penetrance

but gene has variable expressivity among the affected individuals

Question 17

autosomal recessive

Answer 17

age of onset is earlier in life
expression of the defect tends to be more uniform and complete penetrance is common
new mutations do occur but not usually detected bc individual would be a carrier without clinical manifestations
many of these disorders present with enzyme defects that produce inborn errors of metabolism
carriers may possess reduced amounts of the normal enzyme

Question 18

what trait may be carried on y chromosome?

Answer 18

hairy ears

all sexlinked diseases are x-linked

Question 19

x-linked recessive

Answer 19

rarely heterozygous females may demonstrate full expression due to unfavorable lyonization

Question 20

lyonization

Answer 20

all but one x chromosome is randomly activated in all of the cells within zygote- barr body formation within 16 days of conception
either maternal or paternal x may be inactivated in each cell and that x remains inactivated in the progeny of the cell
in disorders of x chromosomes- typically females are an even mixture of normal and abnormal chromosomes
unfavorable lyonization refers to inactivation of an abnormally high percentage of normal x chromosomes- leading to clinical evidence of the disease in a heterozygote

Question 21

x-linked dominant

Answer 21

heteroxygous, homozygous, hemizygous are affected

Question 22

marfan syndrome

Answer 22

autosomal dominant disorder of connective tissue due to mutation of the FBN1 gene, resulting in abnormal fibrillin- glycoprotein necessary for normal elastic fiber production- change consistency of tissue, skin, joint- hyperflexible

Question 23

what is the prevalence of marfan?

Answer 23

1 in 5000

Question 24

clinical appearance of marfan?

Answer 24

tall, thin body habitus with abnormally long legs, arms and fingers- arachnodactyly- spider fingers
dislocation of lens of the eye
aortic aneurysm and dissection leading to heart failure and aortic rupture

Question 25

ehlers-danlos syndrome

Answer 25

6 different types may exist in both dominant and recessive forms problem of collagen synthesis and there are 30 diff types of collagen

Question 26

clinical appearance of ehlers-danlos?

Answer 26

hyperextensible skin and hypermobile joints skn fragility and delayed wound healing rupture of colon, larger arteries hernia

Question 27

familial hypercholesterolemia

Answer 27

disease caused by mutation in receptor proteins mutation in the gene for the LDL receptor (over 900 identified) results in impaired metabolism and increased LDL cholesterol in the plasma causes xanthomas of the skin and premature atherosclerosis

Question 28

frequency of familial hypercholesterolemia

Answer 28

1 in 500 in the population

Question 29

effects of familial hypercholesterolemia

Answer 29

heterozygotes have 2-3x increased cholesterol levels homozygotes have over 5x homozygotes often die of MI before 15 years of age

Question 30

drugs for cholesterol levles

Answer 30

role of LDL receptorbs lef to design statin drugs to control cholesterol levels recent approval of lomitapide to treat homozygous form

Question 31

what is cystic fibrosis

Answer 31

inherited problems with chlorine channels- develop very viscous mucoid secretions that will affect the lung bronchiesctasis- dilations

Question 32

phenylketonuria

Answer 32

disease cause by mutation in enzyme proteins autosomal recessive disorder severe lack of phenylalanine hydroxylase- leading to hyperphenylalaninemia and PKU affected infants are normal at birth, but elevated phenylalanine levels impair brain development, and mental retardation is evident by 6 months of age screening of newborns for this condition is mandatory in the US restriction of dietary phenylalanine intake will prevent the mental retardation

Question 33

rate of phenylketonuria

Answer 33

affects 1 in 10000 caucasian infants

Question 34

lysosomal storage diseases

Answer 34

autosomal recessive transmission commonly affect infants and young children accumulation of insoluble large molecules (sphingolipids and mucopolysaccharides) in macrophages and hepatosplenomegaly frequent cns involvement, mental retardation and or early death

Question 35

examples of lysosomal storage diseases

Answer 35

tay-sachs niemann-pick-single myelin gaucher disease- glycolipids mucopolysaccharidoses

Question 36

mucopolysaccharide storage diseases

Answer 36

most are autosomal recessive traits due to lack of any one of the severa enzymes necessary to degrade mucopolysaccharides affected patients have coarse facial features, clouding of cornea, joint stiffness and mental retardation seven variants

Question 37

hurler disease

Answer 37

deficiency of alpha-l-iduronidase (laronidase) life expectancy of 6-10 years untreated bone marrow transplant or enzyme replacement may improve the outlook but not all aspects of the disease are corrected cost of enzyme >300000 annually

Question 38

hunter syndrome

Answer 38

deficiency of l-iduronate sulfatase x-linked inheritance pattern(males typically affected) absence of corneal clouding and milder clinical course but otherwise similar to hurler syndrome

Question 39

disorders with multifactorial inheritance

Answer 39

many physiologic traits (height, weight, blood pressure, hair color) may underlie common diseases such as diabetes, hypertension, gout, schizophrenia, bipolar disorder two or more genes responsible, plus environmental, nongenetic influences frequency of inheritance ranges from 2-7%

Question 40

what is karyotype?

Answer 40

composite picture o f human chromosome strands can be stained, photographed and arranged in pairs. each chromosome set can be seen to possess distinctive pattern of alternating light and dark bands of variable widths

Question 41

normal karyotupe

Answer 41

23 pairs of chromosome 22 pairs of autosome and 1 pair of sex chromosomes normal chromosome count is 46

Question 42

what number of newborns have chromosomal abnormality? | what percent of 1st trimester spontaneous abortions of fetus have a chromosomal abnormality?

Answer 42

1 in 200 | 50%

Question 43

euploid

Answer 43

normal chromosomal count | 46

Question 44

polyploidy

Answer 44

increased chromosome count that is a multiple of that normally seen

Question 45

aneuploidy

Answer 45

any number that is not an exact multiple of the normal chromosome count

Question 46

trisomy

Answer 46

extra chromosome

Question 47

monosomy

Answer 47

absence of a chromosome

Question 48

structural abnormalities

Answer 48

result from chromosome breakage followed by loss or rearrangement of material

Question 49

translocation

Answer 49

transfer of one part of one chromosome to another nonhomologous chromosome fragments are exchanged between two chromosomes- reciprocal translocation

Question 50

deletion

Answer 50

loss of a portion of a chromosome

Question 51

inversion

Answer 51

chromosome breaks in two points and the released fragment it reunited after a complete turnaround

Question 52

trisomy 21 | down syndrome

Answer 52

most common of the chromosomal disorders associated with advanced maternal age due to meiotic non-disjunction of chromosome 21 during formation of the ovum mental retardation, epicanthic folds, flat facial profile, cardiac malformations, increased susceptibility to infection (including severe periodontal disease in childhood), large tongue, increased prevalence of acute leukemia

Question 53

incidence of down syndrome

Answer 53

45 years 1:25

Question 54

klinefelter syndrome

Answer 54

male hypogonadism that develops when there are at least two x chromosomes and one or more y chromosomes phenotypically male increased length of lower limbs, reduced body hair, gynecomastia, most common reason for hypogonadism dentally- increased frequency of taurodontism

Question 55

turner syndrome

Answer 55

due to partial or complete absence of one of the x chromosomes markedly short stature, webbing of the neck, low posterior hairline, shield like chest, high arched palate, variety of congenital cardiovascular malformations, failure to develop secondary sex characteristics, primary amenorrhea

Question 56

fluorescence in situ hybridization (FISH)

Answer 56

uses fluorescent dye-labeled probes that recognize sequences specific to chromosomal regions

Question 57

comparative genomic hybridization

Answer 57

uses different colored dyes attached to large segments of the test DNA and normal DNA, followed by hybridization relative amts of each DNA sample are assessed based on the color of hybridized product, and gene amplification or deletion can be identified

Question 58

PCR analysis

Answer 58

amplify the DNA in question then compare the order of nucleotides of this DNA to a normal DNA use restriction enzymes and run the segments on gel electrophoresis, compare to normal DNA add fluorescently labeled nucleotides that are complementary to either the wild type or mutant seqeunce, then continue the PCR- determining which nucleotide is incorporated during primer extension

Question 59

indication of dna analysis prenatal

Answer 59

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

Question 60

indication of dna analysis | postnatal

Answer 60

``` multiple congenital anomalies unexplained mental retardation and or developmental delay suspected aneuploidy suspected sex chromosomal abnormality infertility multiple spontaneous abortions ```