Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecules, Genes, and Disease > L4.1 Chromosomal Abnormalities and Prenatal Genetic Testing > Flashcards

L4.1 Chromosomal Abnormalities and Prenatal Genetic Testing Flashcards

You may prefer our related Brainscape-certified flashcards:
Organic Chemistry 101 flashcards
1
Q

Each chromosome consists of

A

proteins and one long molecule of DNA

a short arm (p) and long arm (q) connected by a
centromere

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

A chromatid is

A

one of two identical
halves of a replicated chromosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

A karyotype

A

is the actual picture of an individual’s
collection of chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Karyotypes

A

describe the number of chromosomes and what they look like (size bands and centromere placement)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Karyograms

A

the study of the whole set of chromosomes arranged in pairs by size and position of the centromere

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

chromosome ideogram

A

graphical or schematic representation of chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

G banding

A

a technique used to produce a visible karyotype by staining condensed chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the dark and light bands on the chromosome ideogram numbered according to ?

A

the international convention

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

karyotyping

A

process of pairing and ordering all the chromosomes of an individual

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

karyotyping is also used for what?

A

detect changes in chromosome number and also more subtle structural changes such as chromosomal duplication, deletion, translocation or inversions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are karyotypes prepared from?

A

prepared from mitotic cells that have been arrested in the metaphase or prometaphase of the cell cycle when chromosomes assume their most condensed conformation’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what types of tissue can be used to source karotypes?

A

peripheral blood, amniotic fluid, chronic villus specimens are used as the source of cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

stages from sample to karyotype

A

-collect blood sample
-add phenomagglutnin and culture medium
- culture at 37 degrees for 3 days
-add colchicine and hypertonic saline
cells fixed
-spread cells onto slide by dropping
-digest with trypsin and stain with giesa
-analyse metaphase spread

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

indications for karyotyping

A

a. prenatal screening;
-> down syndrome with raised maternal age, family history of CA, abnormal ultrasound

b. birth defects;
-> malformations or metal impairment

c. Abnormal sexual development
-> Klinefelter or turner syndrome

d. Infertility; recurrent foetal loss
e. Leukaemia or other cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

standard format for karyotyping

A

46, XX or 46, XY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

chromosomal abnormalities

A
  1. Polyploidy
  2. Aneuploidy
  3. Chromosomal mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is Polyploidy

A

more than two complete sets of chromosomes

-> most have an even set of chromosomes e.g. tetraploidy 4n

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is Aneuploidy

A

Aneuploidy is the presence of an abnormal number of chromosomes in a cell. usally 1 more or 1 less.

-> most common chromosomal abnormality and clinically significant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Types of chromosomal mutations

A

deletion
duplication
inversion
insertion
translocation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

how does polyploidy occur in humans?

A

-> very rare in the form of triploid -> 69(XXX) chromosomes or tetraploid with -> 92 (XXXX) chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

why does triploidy occur?

A

due to polyspermy - one oocyte being fertilised by more than 1 sperm.

observed in 1-2% of early miscarriages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

how often does aneuploidy occur in pregnancies ?

A

3-4%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

most common aneuploidies in humans is?

A

trisomy’s which represent 0.3% of all live births

with exceptions - trisomy’s do not appear to compatible with life.

trisomy represent about 35% of spontaneous abortions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

aneuploidy is the most common cause of

A

of the nondisjunction of chromosomes during meiosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

the nondisjunction of chromosomes during meiosis is:

A

is the failure of homologous chromosomes to separate properly during meiotic cell division

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

age for testing for foetal chromosome abnormalities

A

35+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

viable trisomy’s are restricted to only a few human chromosomes; name the conditions and the chromosome number

A
  1. Down syndrome - TRISOMY 21 - viable
  2. Edwards syndrome - TRISOMY 18 - lethal
  3. Patau Syndrome - TRISOMY 13 - lethal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What might be a reason that trisomy 21 is the only viable one?

A

because the number of protein coding sequences predicted for chromosome 21 is the smallest of any chromosome with the exception of Y chromosome

thus the addition of the additional copy of chromosome 21 would be predicted to pertub the normal equilibrium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

3 types of genetic variations that can cause Down syndrome

A

Trisomy 21 - 95% of cases - affects 1 in 800 to 100 births

Mosaic Down syndrome: rare form of down syndrome where a person has only some cells with an extra copy of chromosome 21

Translocation down syndrome - when a portion of chromosome 21 becomes attached or translocated onto another chromosome before or at conception

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Down syndrome features

A

distinct facial features:
flattened face
small head
short neck
protruding tongue
upward slanting eye lids
small ears
poor muscle tone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

More common features of down syndrome

A
  • broad, short hands with a single crease in the palm
  • relatively short fingers - small hands and feet
    excessive flexibility
  • tiny white spots on the coloured parts of the iris - Bushfield’s spots
  • short height
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

symptoms

A

mild to moderate Intellectual disability (low IQ)
congenital heart disease
haematological malignancies
hypothyroidism
gastrointestinal: lack of nerves in the colon (constipation)
infertility
eye disorders: strabismus, refractive errors, cataracts
hearing disorders in 38-78%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Edwards syndrome stats

A

occurs in around 1 in 6000 births
modal lifespan 5-15 days
5-10% of infants survive longer than a year

34
Q

symptoms of Edwards syndrome

A

unusually small head
back of head is prominent
ears are malformed and low set
mouth and jaw are small
clubfeet
hands clenched as fists

heart defects and abnormalities of other organs
that develop before birth

35
Q

Patau syndrome stats

A

1 in 10,000 births 1 in 27,000 live births
5-10% live past their first year
small percentage reach adulthood
multiple congenital abnormalities

36
Q

symptom’s of Patau syndrome

A

severe intellectual disabilities
congenital heart defects
brain or spinal cord abnormalities
very small or poorly developed eyes
low set ears
cleft lip
polydactyly
hypertonia

37
Q

humans are able to tolerate extra sex chromosomes than autosomes why?

A

-> this tolerance most likely relates to both X
-> inactivation and to the small number of genes on the Y chromosome
-> affected individuals generally show reduced sex development and fertility but often have normal life spans and symptoms can be treated with hormones.

38
Q

types of sex chromosome aneuploidies

A

Turner 45, X
Triple X syndrome; 47, XXX
Klinefelter syndrome; 47, XXY
XYY syndrome; 47 XYY

39
Q

X chromosome inactivation

A
40
Q

Chromosomal translocation

A

chromosomes sometimes break and stick to another chromosome

the breakpoints on the two chromosomes often lie between genes

->a person with this translocation will have the full complement of genes; no phenotype

-> risk of passing one of the derivative chromosomes to offspring

-> offspring would be unbalanced and present with a phenotype

41
Q

Robertsonian translocation

A

results from the breakage of two acrocentric chromosomes numbers; numbers 12,14,15,21,22 or close to their centromeres, with subsequent fusion of their long arms to form one chromosome

42
Q

The total chromosome number in a Robertsonian translocation carrier is thus reduced to….

A

45

43
Q

Are Robertsonian translocation carriers normal?

A

yes because there is no gain or loss of important genetic material

44
Q

incidence of Robertsonian translocation

A

1 in 1000 - most common fusion is 13 and 14

45
Q

what is a Philadelphia chromosome

A

results from reciprocal translocation between chromosomes 9 and 22

46
Q

what does the reciprocal translocation in a Philadelphia chromosome cause?

A

the translocation creates a FUSION gene; BRC-ABL

that encodes for a fusion protein BRC-ABL that is oncogenic

47
Q

first line of therapy for individuals with Philadelphia chromosomes BRC-ABL

A

BRC-ABL tyrosine-kinase inhibitors

48
Q

deletion - chromosome abnormalities example

A

chronic lymphocytic leukaemia - deletion of the short arm on chromosome 17 is found in 5-8% of patients and is assoicated with rapid disease progression

49
Q

visualising chromosomes - what technique?

A

FISH - fluorescence in situ hybridization

50
Q

what is FISH

A

-> cytogenetic localisation of DNA sequences

51
Q

outline the process of FISH

A

-> produces a red fluorescent signal at the sites of a specific DNA sequence; in this case; a 150kb segment of chromosome 1

-> several probes each corresponding to a defined genomic segment can be simultaneously analysed and ordered with respect to each other using multicolour FISH

52
Q

Using FISH to detect chromosomal abnormalities in interphase nuclei - CHARCOT MARIE

A

the duplication of a small portion of chromosome 17 that causes CHARCOT MARIE TOOTH SYNDROME is evident by the appearance of three rather than 2 red signals in this nucleus.

53
Q

Using FISH to detect chromosomal abnormalities in interphase nuclei - Philadelphia chromosome

A

is evident by the appearance of the close juxtaposition of one pair of green and red signals

54
Q

visualising chromosomes

A
  • spectral karyotyping and multicolour FISH paint each human chromosome’s in one of 24 colours.
55
Q

M-FISH

A

a 24 colour karyotyping technique and is the method of choice for studying the arrangement of intrachromosomal rearrangements

56
Q

screening

A

is a program applied to a whole population, or large numbers of asymptomatic but potentially at risk individuals

57
Q

testing

A

is applied to either symptomatic individuals to establish diagnosis or asymptomatic individuals with a positive screening test

58
Q

Screening programmes offered during pregnany

A

infectious diseases
inherited conditions
11 physical conditions (20 week scan)
down syndrome, Edwards syndrome, pataus syndrome

59
Q

screening offered for the new born

A

physical exam
hearing screening
blood spot screening

60
Q

Young person and adult screening programmes

A

eye problems in individuals with diabetes
abdominal aortic aneurysms

61
Q

cancer screening programmes

A

cervical screening
breast screening
bowel screening

62
Q

New born blood spot DAY 5 -> heel prick test what does it look for?

A

PKU
congenital hypothyroidism
CF
MCADD
HCU
MSUD
GA1
IVA

63
Q

New-born hearing screening

A

automated otoacoustic emission test
-> quick and non invasive

Earpiece placed into baby ear and gentle clicking noises are played.

-> if results are unclear offered a second test

64
Q

AABR test - further hearing test

A

3 sensors on baby’s head and neck, soft headphones are placed over baby’s ears and gentle clicking noises are played

65
Q

New-born Physical Examination

A
  • offered within 72 hours after birth
    examine: eyes, heart, hips, testicles, back, hands, feet, palate, anus
66
Q

Screening in pregnancy - conditions looked for and treatment

A

Gestational diabetes - OGTT
Preeclampsia - Low dose aspirin
Mental health disorders - specialist services
blood group rhesus factor - Anti D injection

67
Q

Screening for infectious diseases during pregnancy?

A

-> blood test at week 10

3 Infections: Hep B, HIV, and syphilis

treatment to prevent transmission

68
Q

Screening for 11 physical conditions - what happens

A

week 20 scan
-> detailed look at bones, heart, brain, spinal cord, face, kidneys, and abdomen

->sonographer looks for the 11 rare conditions

69
Q

11 rare conditions at 20 week scan

A

anencephaly
open spina bifida
cleft lip
diaphragmatic hernia
gastroschisis
exomphalos
cardiac abnormalities: TGA, AVSD, TOF, HLHS
bilateral renal agenesis
lethal skeletal dysplasia
Edwards syndrome
Patau’s syndrome

70
Q

What does a diaphragmatic hernia look like on a scan?

A

there are multiple air filled loops in the left hemi thorax with mediastinal shift to the right and ipsilateral lung hypoplasia

71
Q

Spina bifida on a scan

A

failure of closure of the vertebral arch at level of L5

72
Q

Down syndrome, Patau’s syndrome, and Edwards syndrome testing:

A

COMBINED TEST at 10-14 weeks
-> Ultrasound scan to check for Nuchal translucency (fluid at the back of the baby’s neck)

-> Blood test: Beta HCG - serum pregnancy assoicated plasma protein A

Combined results of both tests calculate risk for all 3 conditions

73
Q

what happens if the sonographer is unable to see the Nuchal translucency measurement ?

A

at 14-20 weeks they will have:
-> blood test (alpha feta protein, BHCG, unconjugated estriol and inhibin A)
->downs only
->less accurate

74
Q

what is the outcome of the foetal anomaly screening ?

A

higher risk result: offered a diagnostic test to find out for certain whether the baby has down, Edwards, or Patau’s syndrome

75
Q

the use of alpha-fetoprotein (AFP) or USS for prenatal screening for neural tube defects

A

USS is more effective than AFP
The level of AFP is an indicator of potential NTD

76
Q

List the genetic diagnostic tests:

A

Tests and biopsies of the foetus
PCR tests
karyotyping
new developments

77
Q

Foetal DNA screening - who’s DNA is obtain and how is foetal DNA isolated?

A

Parental and sibling DNA collected from blood or saliva

BABYS DNA OBTAINED:
amniotic fluid cells
chorion villus biopsy
foetal DNA in mother blood

78
Q

Amniocentesis - when is it performed, what is done?

A

performed at 15-20 weeks
ultrasound guidance
cells must be recovered and may need to be cultered for 2 weeks

79
Q

Amniocentesis miscarriage rate

A

0.5-1%

80
Q

Chorion villus biopsy- what is it and when is it done?

A

Performed at 10-13 weeks gestation
ultrasound guided
->transcervical or transabdominal
foetal villi must be seerated from maternal tissue

81
Q

Chorion villus biopsy miscarriage rate

A

2%

82
Q

NIPT - Non-invasive prenatal testing : what is it ?

A

Foetal DNA can be isolated from the mothers blood along with the mothers own DNA

If the mother and father have been typed for particular disease causing mutations the foetal status can be derived from sequencing the isolated DNA

-> can be offered to women who had a higher change results form combined or quadruple test

Molecules, Genes, and Disease (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions