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Flashcards in Week 1 Genetics Deck (88):
1

What is the cause of abnormalities in chromosome number?

nondisjunction

2

What is nondisjunction?

Error in cell division where improper segregation leads to abnormal chromosome number

3

When does nondisjunction typically occur?

It can occur in any cell division:
- Meiosis I
-Meiosis II
-Mitosis

4

Maternal age effect is associated with nondisjunction in what phase of cell division?

meiosis I

5

Mosaicism is associated with nondisjunction in what phase of cell division?

Mitosis

6

What is the word for normal chromosome number?

Eupolid
Haploid (23 for gametes)
Diploid (46 for somites)

7

What is the word for chromosome numbers that are NOT multiples of 23?

Aneupolid
Monosomy (if 45)
Trisomy (if 47)

8

What is the word for entire extra sets of chromosomes?

Polyploid
Triploidy (1 extra set)
Tetraploidy (2 extra sets)

9

What is the cause of triploidy?

Dispermy (fertilization by 2 sperm)

10

What is the cause of tetraploidy?

failure of cell division

11

Are polyploids viable?

NO, common at conception and common cause of spontaneous abortion

12

True or false, all monosomies of autosomes are lethal.

TRUE

13

True or false, all trisomies of autosomes are lethal.

FALSE

14

List the clinically signficiant, viable trisomies.

13
18
21

15

True or false, aneuploidy is common in gametes but rarely present in live births.

True, it is only present in around 3% of births, because aneuploid offspring are typically lost very early (before the 1st trimester)

16

What is the leading cause of spontaneous abortion?

chromosome abnomalities (50% of miscarriages, 90% of losses in very early pregnancies)

17

True or false. Fetuses with Turner's syndrome are rarely spontaneously aborted.

FALSE. Around 20% of Fetuses with monosomy X are spontaneously aborted.

18

True or false. Autosomal monosomies commonly result in spontaneous abortions.

FALSE. Autosomal monosomies only account for 1% of spontaneous abortions, these are lost before clinical recognition of pregnancy in most cases

19

What is another name for trisomy 21?

Down Syndrome
*Most common chromosomal disorder

20

What is the most common cause of Trisomy 21? Second most common cause?

95% Nondisjunction (maternal meiosis I) wtih 2-4% exhibiting mosaicism

5% translocation (Robertsonian)

21

What are the 2 ways mosaicism can occur in Trisomy 21?

Normal conception, early in development nondisjunction occurs and leads to trisomy cell line.

Trisomy 21 conception, early in development cell loses one of the 21's and this cell line becomes dominant (have increased level of survival and milder phenotype!)

22

True or false: trisomy 21 is more common in males.

FALSE- equally common in males and females

23

What is the incidence of trisomy 21?

1 in 800 live births
only around 20% live until live birth

24

What is another name for trisomy 18?

Edward's syndrome

25

What are the major clinical findings of infants with trisomy 18?

mental retardation
rocker bottom feet
Clenched hand
Life expectancy of less than 1 year

26

What is the major cause of trisomy 18?

maternal nondisjunction

27

What is the incidence of trisomy 18?

1 in 6000
less than 5% of conceptions survive to term

28

What is another name for trisomy 13?

Patau syndrome
Most severe of the viable trisomies

29

What are the major clinical findings of infants with trisomy 13?

Abnormal midline development (cleft lip, omphalocele, etc.)
Poldactyly
Severe mental retardation
Very short life expectancy

30

What is the major cause of trisomy 13?

80% due to meiotic nondisjunciton (maternal age effect)
20% Robertsonian translocation
Mosiacism is rare

31

What is the incidence of trisomy 13?

1 in 10,000 live births
Less than 5% of conceptions survive to term

32

True or false: 1 in 500 people have a sex chromosome abnormality.

True- less severe phenotypes are seen in sex chromosomes

33

What is another name for monosomy X?

Turner's syndrome

34

What are the major causes of Turner's syndrome?

50% meiotic nondisjunction (80% PATERNAL)
35% mosaic
5% mosaic with Y-bearing cell line (started off male at conception but nondisjunction event very early)
10% structural abnormalities in X chromosome

35

What is the consequence of 5% of Turner's syndrome patients being mosaic with Y-bearing cell line?

they are at increased risk for certain cancers

36

What is the incidence of monosomy X?

1 in 2500 live births
1-2% of conceptions, where 99% are lost

37

What is XXY?

Klinefelter Syndrome

38

What is the major cause of XXY?

50% Paternal nondisjunciton
50% maternal nondisjunction

39

What is the incidence of XXY?

1 in 1000 male live births
50% spontaneously aborted

40

What is the incidence of trisomy X?

1 in 1000 female live births

41

What is the major cause of trisomy X?

90% maternal nondisjunction with age effect

42

What is the incidence of XYY?

1 in 1000 male live births

43

What is interesting about XYY?

It only has 1 possible cause

44

What is the cause of XYY?

Paternal meiosis II nondisjunciton (NO age effect)

45

True or false: a Karyotype is a screening test.

FALSE: Karyotypes are diagnostic tests

46

How quickly can you get a karyotype after CVS or aminocentesis?

7-10 days

47

When can a CVS be performed?

late in the 1st trimester

48

What is a CVS?

chorionic villus sampling- involves transabdominal or transcervical aspiration of chorionic villi from the developing PLACENTA

49

When can an aminocentesis be performed?

at 15-17 weeks

50

What is an amniocentesis?

the extraction of epitheloid cells shed from the amnion and lower fetal urinary tract from AMNIOTIC FLUID

51

What is the major contamination risk associated with invasive techniques?

you could accidently extract maternal cells and grow them in culture to get your karyotype

52

True or false: FISH is a screening test.

TRUE- it is a screening test that utilizes specific DNA probes hybridized to patient's chromosomes

53

Chromosomes used for a FISH test must be in what phases?

interphase or metaphase

54

How do you get the fetal chromosomes for FISH?

aminocentesis

55

How quickly can you get results from a FISH?

within 1-2 days

56

What does a FISH tell you?

it tells you if you have common aneuploidies that the probes tested for

57

True or false: NIPS is a screening test.

TRUE: Noninvasive prenatal screening for fetal aneuploidy requires amniocentesis for confirmation after a positive result

58

What is NIPS?

a method that takes advantage of the 10% cfDNA (fetal) in maternal serum to test for specific aneuploidies (21, 18, 13, Y) with HIGH predictive value

59

When can NIPS be performed?

10 weeks

60

Describe a metacentric chromosome.

short (p) arm is only slightly shorter than the long (q) arm

61

Describe a submetacentric chromosome.

p arm is MUCH shorter than q arm

62

Describe an acrocentric chromsome.

p arm is tiny and completely composed of repeated sequences of rRNA genes that are redundant and unnecessary for survival if others are present

63

What word describes a novel rearrangement containing the net normal amount of genetic material?

balanced

64

What word describes a rearrangement associated with extra and/or missing genetic material?

unbalanced

65

What are common phenotypic abnormalities seen with unbalanced rearrangements?

-Developmental delay (intellectual disability)
-Growth delay
-Facial dysmorphology/physical malformations
-Congenital organ malformations (ex. heart defects)

66

True or false: an inversion is an example of an unbalanced rearrangement.

FALSE- inversions are balanced.
Deletions, duplications, isochromosomes, and ring chromosomes are unbalanced

67

What is the difference between pericentric and paracentric inversions?

pericentric involves the centromere
paracentric is an inversion on the SAME arm

68

Severity of unbalanced phenotype depends on what factors?

-Mosaicism (if you have a normal genome mixed in phenotype is milder)
-Sex versus somatic chromosome (milder phenotype with sex chromosomes)
-Size of imbalance (larger is more severe--potentially lethal)
-Monosomy versus trisomy (monosomy is WAY more severe)

69

What is the difference between an acentric fragment and a centric fragment?

acentric fragments do NOT contain a centromere, centric fragemnts DO contain a centromere

70

What provides a more stable translocation products, acentric exchange or centric exchange?

acentric fragments, if exchanged, produce chromosomes that are stable in meiosis

if a centric fragment is exchanged with an acentric fragment, you will get 1 chromosome with 0 centrosomes and 1 chromosome with 2 centrosomes--neither of which are stable in meiosis

71

What types of chromosomes undergo Robertsonian translocations?

acocentric: 13, 14, 15, 21, 22

72

What increases the risk of unbalanced gametes in a person with a balanced reciprocal translocation?

abnormal segregation during meiosis via the "adjacent" pattern where gamete receives one structurally normal chromosome and one abnormal chromosome

73

What is the consequence of "adjacent" segregation pattern?

"duplication, deletion" with partial trisomy, partial monosomy, and high risk for phenotypic abnormalities or miscarriage

74

What would you expect to see on a karyotype of someone with a Robertsonian translocation?

45 chromosomes (where one is the LONG ARM of 2 acrocentric chromosomes fused together)

75

What are the possible outcomes of gametes from segregation in a person with a Robertsonian translocation?

Normal offspring
-both normal chromosomes
Balanced offspring
-one Robertsonian chromosome
Monosomy
-one copy of normal
Duplication, Deletion
-one normal and one Robertsonian

76

What is an impossible outcome of offspring of a person with Robertsonian translocation?

Unbalanced offspring:
-either balanced/normal
OR
-nonviable

77

What is translocation Down's syndrome?

when a woman (more likely) with a Robertsonian translocation (involving 13 and 21) have gamete segregation, nondisjunction occurs with the Robertsonian leading to one normal 21 and one Robertsonian chromosome getting packaged. This leads to trisomy 21 in the offspring.

78

What is a Homologous Robertsonian?

when a centromere misdivision leads to the fusion of two copies of the long arm of the SAME acrocentric chromosome

79

What are the phenotypes of offspring from a person with a homologous Robertsonian?

0% change of healthy offspring, either have a trisomy (ex. Turner's syndrome or Down's syndrome) or a monosomy (nonviable)

80

What is a microdeletion?

a partial monosomy that is too small for reliable detection by routine methods (ex. karyotype)

81

What is deleted in a microdeletion?

multiple, adjacent genes in a "critical region"

82

What causes microdeletions?

improper matching of "low copy repeats" that surround a critical region and lead to improper crossing over (forming 1 chromosome with 2 critical regions and 1 chromosome with 0 critical regions)

83

What disease is caused by an interstitial microdeletion encompassing 15q12?

Prader-Willi Syndrome

84

What is the phenotype of an infant with Prader-Willi syndrome?

hypotonia in infancy
childhood hyperphagia
obesity
mental retardation

85

True or False: negative results of a FISH test for a microdeletion rules out disease.

FALSE, FISH is a good way to confirm a diagnosis but negative results are of limited use

86

What is recommended as a first tier diagnostic test for individuals with developmental disabilities or congenital abnormalities?

CMA (Chromosomal Microarray)

87

What is a CMA?

Method that assays the entire genome for regions of imbalance (higher yield than karyotype, better detection of duplications than FISH, very precise characterization of abnormality)

88

What are the limitations of CMA?

cannot detect:
balanced rearrangments
some polyploidies
point mutations