Quiz4_biochem20130928 Flashcards

2
Q

Features of chromosome behavior

A

segregation, independent assortment, recombination

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3
Q

Law of segregation

A

allele pairs separate during gamete formation

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4
Q

principle of independent assortment

A

alleles of different genes assort & are passed independently of one another from parents to offspring during gamete formation; complicated by linkage

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5
Q

Linkage

A

tendency of genes located proximal to each other on a chromosome to be inherited together during meiosis

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6
Q

recombination

A

production of new combinations of alleles encoding a novel set of genetic information (e.g. homologous chromosomal crossing over); any meiotic process generating a haploid product with a genotype differing from that constituted in the meiotic diploid cell

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7
Q

recombinant frequency

A

total number recombinants/total number progeny; note: independent assortment always produces RF of 50%; RF 50% in test cross indicates that the two genes under study assort independently

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8
Q

LOD score

A

statistical test for linkage analysis to test whether segregation data from family studies indicates linkage btwn 2 loci or if just due to random segretation

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9
Q

LOD score of 3 or more

A

indicates linkage, _ at which LOD is highest is the most likely genetic distance btwn the two loci

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10
Q

LOD score of -2 or less

A

indicates no linkage

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11
Q

Association

A

co-occurrence of a disease and a genetic marker more often than expected by chance in a population

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12
Q

Linkage vs Association

A

(1) L must be in families/A can be in unrelated individuals; (2) L is btwn loci/A is btwn specific alleles of loci; (3) A may imply causal/physiological relationship btwn disease and allele/L does not

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13
Q

monogenic genetic disorder

A

mutation in 1 gene

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14
Q

chromosomal genetic disorder

A

increase/decrease in copy # of whole chromosomes or chromosomal regions rich in genes

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15
Q

mitochondrial genetic disorder

A

defects in mtDNA

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16
Q

multifactorial genetic disorder

A

interplay of multiple genes & multiple environmental factors

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17
Q

somatic genetic disorder

A

series of genomic changes in somatic cells over time -> not passed to offspring

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18
Q

Product rule

A

probability of 2 indpendent events occurring simultaneously

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19
Q

Sum rule

A

probability of either one of the 2 independent events occurring

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20
Q

Autosomal dominant disorder

A

Normal allele sufficient to compensate for mutant allele; Heterozygotes affected; phenotype appears in every generation (vertical transmission); each child has 50% recurrence risk; males & females equally likely to transmit trait

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21
Q

Gain of fx

A

mutant gene product has increased or novel activity over normal gene product

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22
Q

Dominant negative

A

mutant gene product inhibits activity of normal gene product

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23
Q

Haploinsufficiency

A

half of expression from single normal allele is not nenough protein

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24
Q

Autosomal recessive disorder

A

both alleles of gene must be defective to cause visible phenotype/disease state; affected individuals homozygous for disease -> both parents must be unaffected heterozygous carriers; if appears in >1 family member typically seen among siblings (horizontal transmission); recurrence risk for each sibling of proband 25%; males & females equally likely to be affected; more common in consanguinity

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25
Q

Loss of fx

A

inactivation of gene at molecular level

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26
Q

X inactivation

A

achieves dosage compensation btwn males and females for critical X-linked genes -> transcriptional silencing of one of the X chromosomes in females (DNA methylation)-> Barr body

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27
Q

genes at distal tip of short arm of X chromosome

A

do not undergo inactivation (up to 15% of genes) -> candidates for clinical phenotype associated with numerical abnormalities of X chromosome

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28
Q

X-linked dominant

A

few in number; vertical transmission pattern; NO male to male transmission; 2x as common in females

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29
Q

X-linked recessive

A

females: both copies of X must be defective; males hemizygous for X -> inherit only from mother; gene responsible transmitted from affected man to his daughters -> heterozygous carriers: daughters’ sons have 50% chance of inheriting disease

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30
Q

How can a heterozygous female express an X-linked recessive trait

A

mosaicism/skewed X-inactivation

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31
Q

Y-linked

A

no known diseases; expected: male to male transmission, only males affected

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32
Q

Hardy-Weinberg population frequencies

A

p^2 + 2pq + q^2 = 1; p+q =1

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33
Q

consanguinity

A

of same kin/mating of related individuals; present more frequently in pedigrees w/ autosomal recessive diseases; increases risk of mating couple both carrying same disease allele

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34
Q

factors complicating inheritance patterns

A

new mutations, germline mosaicism, delayed age of onset, reduced penetrance, variable expressivity, genetic heterogeneity, locus heterogeneity, allelic heterogeneity

35
Q

germline mosaicism

A

all or part of germ cells have disease mutation, somatic cells normal (parent is non-expressorm risk of affecting multiple offspring)

36
Q

reduced penetrance

A

individual w/ genotype for disease does not exhibit disease phenotype; can transmit disease to offspring

37
Q

variable expressivity

A

complete penetrance, but severity differs among affected family members w/ same mutation

38
Q

locus heterogeneity

A

disease that can be caused by mutations at different loci in different families

39
Q

allelic heterogeneity

A

different mutations in same gene result in similar phenotypes

40
Q

genetic heterogeneity

A

single phenotype/disorder may be caused by any one of a multiple number of alleles or non-allele mutations

41
Q

Fragile X syndrome

A

constriction/gap at end of long arm of X chromosome = fragile site; 5’ UTR FMR1 contains tandem repeated trinucleotide sequence (CGG) of variable length; expansion of repeat occurs during meiosis; 6-50 repeats = normal; 50-200 repeats = premutations; >230 repeats = affected

42
Q

Dynamic mutations

A

repeat expansion results in genetic disease once number of repeats reaches a threshold -> leads to changes in gene function

43
Q

genetic anticipation

A

increasing severity & earlier onset of disease w/ each passing generation; correlated with increased # of repeats

44
Q

constitutional chromosome abnormalities

A

inherited, found in all body tissues

45
Q

acquired chromosome abnormalities

A

not inherited, typically only in 1 tissue

46
Q

FISH

A

detect & localize presence/absence of specific DNA sequences on chormosomes using sequence specific probes (complementarity)

47
Q

whole chromosome paints

A

used to spot de novo translocations

48
Q

Alphoid repeats

A

interphase FISH, chromosome specific centromeric repeat sequences have intense tight signals

49
Q

aneuploidy

A

abnormal chromosome number

50
Q

Trisomy 21

A

nondisjunction in meiosis I or II; if 2/3 chromosomes are same -> Meiosis II; if all 3 chromosomes different -> Meiosis I

51
Q

Robertsonian translocation

A

long arms of 2 acrocentric chromosomes fused at centromeres -> loss of short arms; carrier is normal, risk to offspring

52
Q

Mosaicism

A

nondisjuntion in mitosis resulting in 2 different cell lines (e.g. normal and trisomy)

53
Q

Polyploidy

A

any multiple of haploid chromosome number; extra chromosome set is paternally derived

54
Q

Reciprocal translocation

A

breakage of nonhomologous chromosomes w/ reciprocal exchange of chromosomal material; carrier normal, risk for unbalanced gametes & abnormal offspring

55
Q

Balanced structural mutations

A

no loss/gain of genetic material, no phenotypic effect; risk for unbalanced gametes; translocation or inversion

56
Q

terminal deletion

A

1 break, loss of material distal to break point

57
Q

Unbalanced structural mutations

A

loss/gain of genetic material, severe phenotypic effects; deletions

58
Q

interstitial deletion

A

2 breaks, loss of material between breaks

59
Q

Prader-Willi syndrome

A

paternal deletion; maternal unpaired disomy; imprinting center mutation on paternal allele

60
Q

Angelman syndrome

A

maternal deletion; paternal unpaired disomy, imprinting center mutation on maternal allele

61
Q

Duplication

A

results from unequal crossing over

62
Q

Turner syndrome

A

X chromosome monosomy; X0; paternal nondisjunction (45,x); mosaicism 45,x/46,xx or 45,x/46,xy

63
Q

Klinefelter syndrome

A

X chromosome trisomy; 47, XXY; extra X of maternal origin; mosiacism 46,XY/47,XXY

64
Q

47, XXX

A

maternal nondisjunction, increased incidence w/ AMA

65
Q

47, XXY

A

NOT result of maternal nondisjunction, no increased incidence w/ AMA

66
Q

cancer cytogenetics

A

acquired chromosomal abnormalities in hematologic malignancies; chromosome rearrangements may alter position of genes -> alteration of gene product may cause malignancy

67
Q

functional approach to identify disease genes

A

based on knowledge of specific protein product of gene, use recombinant DNA technology to isolate genes

68
Q

candidate gene approach to identify disease genes

A

test DNA coding sequence for protein mutations in affected individuals, no genetic mapping required

69
Q

positional candidate approach to identify disease genes

A

mapping of disease gene to correct chromosomal subregion via linkage analysis

70
Q

linkage analysis process

A

use of annotated sequence showing genetic markers -> focus on genetic region of interest -> identify & rank candidate genes -> assay candidate genes

71
Q

units for linkage analysis

A

1cM = 1% recombination frequency = 10^6 bp DNA

72
Q

marker

A

polymorphism used to follow a disease gene family -> not related to etiology of disease

73
Q

direct genetic testing

A

identify specific mutation in affected individuals

74
Q

indirect genetic testing

A

determine if individual has inherited a chromosome containing disease gene from either parent using genetically linked markers

75
Q

Limitations to sanger/exome sequencing

A

does not detect most structural changes (large deletions), false negative results (sequence alteration exists in another gene at another locus or in a region not covered by test)

76
Q

Benefits of sanger/exome sequencing

A

detects changes in coding region of gene, detects documented pathogenic alteration, unknown sequence alteration, documented benign polymorphisms, undocumented sequence predicted to be benign

77
Q

Multiple PCR analysis

A

simultaneous amplification of everal exons/regions of interest of gene; evaluate products for presence/absence of specific regions amplified, detect deletion of specifc exons of disease

78
Q

Allele specific oligonucleotide analysis

A

direct gene diagnosis of single nucleotide change for known mutations (automated), 1st ASO oligonucleotide that will hybridize only to mutated sequence, 2nd ASO hybridizes to corresponding normal sequence (control); idnetify genotype of individuals w/ regard to mutation specified by probe

79
Q

microarray analysis

A

probe expression of 1000s of genes simultaneously to investigate differential expression of genes w/ potential relevance to wide range of disease processes (uses mRNA or cDNA)

80
Q

Array-CGH

A

comparative genomic hybridization; high res alanylsis of copy number variations (gain/loss) at molecular level; can detect microdeletions and duplications

81
Q

advantages of array-cgh

A

no dividing cells required, whole genome analysis in 1 experiment, fast, cost-effective, automated, high res analysis - tests multiple loci

82
Q

limitations of array-cgh

A

sensitivity & quality of analysis depend on probes selected, balanced rearrangements NOT detected (only gain/loss), distinguishing between benign from disease-causing gains/losses requires parental studies