Brainscape's Knowledge GenomeTM

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


See full index

Clinical Genetics > Chromosomal Abnormalities I > Flashcards

Chromosomal Abnormalities I Flashcards

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

What are histones?

A

Histones are highly positively charged proteins attracted to negatively charged DNA

They give DNA support to wrap around

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

What is a chromosome?

A

An organized package of DNA found in the cell nucleus

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

Describe the structure of chromosomes

A

Chromosomes usually exists as chromatin

DNA double helix binds to histones

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

What is a nucleosome?

A

DNA wrapped around octamer of histones form nucleosome

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

What are features of euchromatin?

A

Extended state, dispersed through nucleus

Allows gene expression

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

Describe heterochromatin

A

Highly condensed, genes not expressed

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

Why is DNA loosely packed?

A

DNA usually loosely packed to enable TF to bind for protein expression

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

When is DNA tightly coiled?

A

During cell division DNA is complexed with various proteins and undergoes several levels of compaction through coiling and supercoiling

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

How many chromosomes do we have?

A

Humans have 23 homologous pairs of chromosomes

- 1 from each parent

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

What is locus?

A

Locus: any given position on a chromosome

Can be used to define a single base or a genomic region

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

Describe loci on homologous chromosomes

A

Homologous chromosomes have identical loci of genes with varying allelic forms - loci should match up; significant in meiosis (metaphase) where chromosomes line up

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

What enables genetic variation?

A

Dominant and recessive forms of genes give genetic variation

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

Outline how chromosomes go from single chromatids to sister chromatids

A

During interphase of cell cycle a single chromatid is produced after cell division has occurred in G1

S1 duplicates DNA products from G1 to produce identical sister chromatids

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

Describe what occurs during G1 of cell cycle?

A

G1 = Cell makes a variety of proteins needed for DNA replication

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

What happens in S phase?

A

S = synthesis; chromosomes are replicated so that each chromosome now consists of two sister, identical chromatids

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

What occurs in cell cycle phase of G2?

A

G2 – synthesis of proteins especially microtubules

Some cells don’t replicate; some are senescent. Undergoes error checks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do loci and gene content differ in chromatids and homologous chromosomes?

A

Loci and gene content is identical in sister chromatids

In homologous chromosomes gene loci and content is also similar but may have varying allelic forms (dominant / recessive)

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

Describe the normal human karyotype

A

Humans have 23 pairs of chromosomes

22 pairs autosomes, 1 pair sex chromosomes XX or XY

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

What is the best time to view chromosomes under microscopes?

A

Sister chromatids in metaphase of meiosis are easier to visualise under a microscope as they’re more condensed

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

What are metacentric chromosomes?

A

Metacentric

  • p & q arms even length
  • 1-3, 16-18
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are submetacentric chromosomes?

A

Submetacentric

  • p arm shorter than q
  • 4-12, 19-20, X
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are accrocentric chromosomes?

A

Acrocentric

  • Long q, small p
  • p contains no unique DNA
  • 13-15, 21-22, Y
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Why do all cells not have 23 perfect pairs of chromosomes?

A

Not all cells have 23 pairs of perfect chromosomes e.g:

  • Mutations: trisomy abnormalities
  • Gametes have 23 single chromosomes (haploid)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the 2 types of chromosomal changes that can occur?

A

There are 2 categories of genome changes that can occur:

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

What is haploid?

A

HAPLOID: one set of chromosomes (n=23) as in a normal gamete.

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

What is a diploid no.?

A

DIPLOID: cell contains two sets of chromosomes (2n=46; normal in human)

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

What does polyploid mean?

A

POLYPLOID: multiple of the haploid number (e.g. 4n=92)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is meant by aneuploid?

A

ANEUPLOID: chromosome number which is not an exact multiple of haploid number - due to extra or missing chromosome(s) (e.g. 2n+1=47)

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

What are the common chromosomal numerical abnormalities?

A

Trisomy
Monosomy
Mosaicism

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

What is disjunction?

A

Pulling apart at anaphase = disjunction

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

What are the 2 phases of meiosis

A

Meiosis I

Meiosis II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Describe what occurs in meiosis I

A

Meiosis I - allelic recombination

  • Generates variations
  • Important homologous chromosomes line up correctly at equator for recombination to occur
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What happens during in meiosis II?

A

Meiosis II - chromatids disjunction

- Haploid daughter cells with genetic variation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What happens during mitosis?

A

Single round of cell division

Produces diploid daughter cells with identical genetic info

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is the mechanism responsible for aneuploidy

A

Primary mechanism = nondisjunction; chromosomes don’t separate correctly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Describe how aneuploidy arises in meiosis I

A
  1. Nondisjunction in M1 = both chromosomes end up in
    same daughter cell
  2. M2 occurs normally but a daughter cell will end up
    with 2 copies of nondisjunction chr. ⇒ disomic
  3. Another daughter cell will lack both normal chr. pairs ⇒
    nullisomic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

How does aneuploidy in Meiosis II arise?

A
  1. Nondisjunction in M2 = chr. pulled apart and entered
    one gamete as opposed to being split between two
  2. One gamete will be disomic and another nullisomic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are the products of fertilisation of nondisjunction products?

A

Fertilisation occurs producing:

  • Trisomies (3 copies of chr.)
  • Monosomies (single chr. copy)
  • Disomies (2 copies of chr.) normal
39
Q

Name the classic autosomal trisomies

A

Trisomies 13, 18 and 21 are classic autosomal trisomies (Patau’s, Edwards & Down’s)

40
Q

Why do we not see autosomal trisomies other than 13,18 and 21?

A

Other chromosomal meiotic trisomies can occur but those pregnancies don’t continue to full term

41
Q

What is the DNA content in mitotic nondisjunction?

A

Mitotic NDJ; majority of cells 2n some 2n+1 = mosaic

42
Q

How does mitotic NDJ occur?

A

Zygote generated with correct no. of diploid chr. But at some point during mitotic cell division nondisjunction occurs

43
Q

Describe the chromosome content of mitotic NDJ daughter cells

A

The daughter cell produces 3 copies of chr. while another daughter cell will have just one copy

44
Q

What is the consequence of mitotic nondisjunction?

A

As these cells continue to divide, all cells originating from the trisomic daughter cell will also be trisomic and same for the monosomic daughter cells

45
Q

What is the fate of monosomies?

A

Typically the monosomic cells won’t be maintained and are destroyed

46
Q

What is the fate of trisomies?

A

Some trisomic cells are maintained and so some of the zygotic cells will be trisomic and others will be standard disomic ⇒ mosaicism will present as Down’s (less severe than meiotic Trisomy 21)

47
Q

What is mosaicism?

A

The presence of 2 or more genetically different cell line derived from a single zygote

48
Q

What are the 2 mosaicism mechanisms?

A

Postzygotic nondisjunction

  • Mitotic nondisjunction
  • All 2n to mixture of 2n and 2n+1

Anaphase lag

  • Trisomic rescue
  • All 2n+1 become a mixture of 2n+1 and 2n
49
Q

What is the clinical relevance of mosaicism?

A

Mosaic phenotype thought to be less severe

Difficult to assess:

  • What are proportions of different cell types?
  • Which tissues/organs affected?
50
Q

Give examples of mosaicism disorders

A

Down ~2% (trisomy 21 / normal)
Klinefelter 15% (46 XY / 47 XXY)
Turner <25%

51
Q

How do mitotic and meiotic nondisjunction disorders differ?

A

Sex chromosomal abnormalities are typically far less severe than autosomal chromosomal abnormalities

52
Q

What is a common monosomy?

A

Relatively common sex chromosome monosomy = Turner’s

53
Q

How does full monosomies arise?

A

Full monosomy arise by NDJ

54
Q

What causes partial monosomies?

A

Partial monosomy (microdeletion syndromes) far more common – mechanism different

55
Q

Describe the clinical significance of monosomies and trisomies

A

Trisomies are detrimental to health, but monosomies are far worse and more lethal

56
Q

Describe turner mosaicism

A

45X / 46XY mosaicism - usually normal male (90%) but with potential for gonadoblastoma

57
Q

What is variant turners syndrome?

A

Mosaicism with ring or isochromosome Xq results in variant Turner Syndrome

58
Q

What are the possible combinations for Turners

A

45X0 or mosaic (45X0/46XX)

59
Q

Outline the incidence of turners

A

Incidence 1/4000 female births

60
Q

What are the effects of turners?

A
  • Raised nuchal translucency
  • Short stature
  • Infertility secondary to gonadal dysgenesis
  • Intellectually normal

At birth:

  • oedema of hands and feet
  • Neck webbing
  • ?coarctation (narrowing) of aorta
  • ?renal malformation
61
Q

What is nuchal translucency?

A

Nuchal translucency is a collection of fluid under the skin at the back of your baby’s neck

62
Q

What is cystic hygroma?

A

A cystic hygroma is a collection fluid-filled sacs known as cysts that result from a malformation in the lymphatic system

63
Q

How does Turners XO arise?

A

Nullisomic gametes due to NDJ fertilised with a sperm carrying an X chromosome will be XO (Turners)

64
Q

How does YO turners arise?

A

Nullisomic gametes fertilised with a sperm carrying a Y chromosome will be YO

65
Q

What is the result of disomic gametes fertilising to form Turners

A

Disomic gametes fertilise to become either XXY or XXX trisomies

66
Q

What are the possible nullisomic Turners combinations

A

Nullisomic gametes

+X chr = XO = Turner’s (physically female)

+Y chr = YO = lethal

67
Q

Outline the possible disomic combinations in Turners

A

XX
+X chr = XXX = triple X syndrome
+Y chr = XXY = Klinefelter’s (physically male)

XY
+X chr = XXY = Klinefelter’s
+Y chr = XYY = XYY syndrome

68
Q

What are the autosomal numerical abnormalities?

A

Trisomy 13, 18, 21

69
Q

What are the common sex chromosome abnormalities?

A

XO, XXY, XYY

70
Q

How do we identify and test for numerical abnormalities?

A

Access blood and culture mitotic (metaphase) cells to identify abnormal karyotypes

71
Q

Which cell type is used to produce a karytotype?

A

Pretty much any nucleated cell can be used – e.g. skin, bone marrow, amniotic cells, CVS, but generally lymphocytes are used

72
Q

Describe chorionic villus sampling

A
  • Done at 11-14 weeks
  • Miscarriage rate 0.5% to 1%
  • Risk of maternal cell contamination
  • Risk of transverse limb defects
73
Q

Outline amniocentesis prenatal diagnosis technique

A
  • Carried out at >16 weeks
  • Extraction of amniotic fluid
  • Biochemical diagnosis possible
  • Miscarriage risk (0.5-1%)
74
Q

What is G-banding?

A

Using a Giemsa stain on chromosomes in Metaphase

75
Q

What is the G-banding line up dependent on?

A

Line-up based on

  • Size
  • Banding due to chromatin makeup
  • Centromere position
76
Q

What does the giemsa stain highlight?

A

Giemsa highlights heterochromatic regions which are less likely to contain genes

77
Q

What is the used of G-banding?

A

The banding is used to differentiate between chromosomes and to compare chromosomes

78
Q

What is identified from a karyotype?

A

When identifying individuals with abnormal karyotypes need to outline the following:

  • No. of chromosomes
  • Sex
  • Abnormal chr.
79
Q

Describe the features of FISH

A

Fluorescent in situ hybridisation
Cultured cells, metaphase spread
Microscopic (5-10Mb)

80
Q

Describe how FISH is carried out

A
  1. Fluorescent probe
  2. Denature probe and target DNA
  3. Mix probe and target DNA
  4. Probe binds to target
81
Q

Why is FISH a long process?

A

because it uses cultured cells, this takes longer than QF-PCR

82
Q

What is FISH?

A

Fluorescence in situ hybridization (FISH) is a molecular diagnostic technique utilizing labeled DNA probes to detect or confirm gene or chromosome abnormalities

83
Q

What is the significance of microsatellites in QF-PCR

A

Microsatellites are typically not associated with disease - just normal genetic variation but can be used in a diagnostic manner in QF-PCR

84
Q

Why are microsatellites used in QF-PCR?

A

We all have copies of these microsatellites but have differing alleles as these are length variations

Designed to be quicker in diagnosing than FISH

85
Q

Describe invasive foetal testing techniques

A

Invasive

  • Amniocentesis (14-20 wks, amniotic fluid)
  • Chorionic villus sampling (CVS) (11-14 wks, placental cells)
86
Q

What are the non-invasive foetal testing methods?

A

Non-invasive

  • Cell free foetal DNA (cffDNA): DNA fragments in maternal plasma (10 wks onwards)
  • For trisomies still need confirmation with amnio/CVS
87
Q

Outline the mechanisms responsible for Downs (trisomy 21)

A

95% NDJ (usually maternal meiosis I)
5% Robertsonian translocation involving chr.21
~2% mosaic

‘Older Egg Model’ – maternal age effect

88
Q

Outline features of Trisomy 21 ‘Downs’

A
  • 1 in 650-1000 live births
  • Most common cause of mental retardation
  • Hypotonia, particularly in newborn period
  • Developmental delay
  • Cardiac abnormalities
  • GI abnormalities
  • Acute Lymphocytic Leukaemia/Acute Myeloid Leukaemia – 10-20 x relative risk
  • Conductive hearing loss
  • Features of Alzheimer’s >40 years
89
Q

Outline features of Trisomy 13 {Pataus)

A 
~1 in 10 000 live births
Midline defects
- Hypotelorism
- Holoprosencephaly
- Midline cleft lip/palate
- Scalp defects
Post axial polydactyly
Heart defects/renal abnormalities
90
Q

Outline features of Trisomy 18 (Edwards)

A
  • Incidence ~1 in 6000 live births
  • Intrauterine growth retardation
  • Micrognathia
  • Cleft lip +/- palate
  • Short palpebral fissures
  • Fixed flexion deformities of fingers
  • Heart defect >95%
  • Inguinal/diaphragmatic herniae
  • Renal malformations
91
Q

Outline the survival rates in Edwards

A

Survival rates in Edwards Syndrome:

  • 30% die by 1 month
  • 50% die by 2 months
  • 90% by 1 year
92
Q

What caues kleinefelters?

A

NDJ paternal meiosis I (50%), others NDJ maternal meiosis or zygotic mitotic error (mosaic)
Variants: 48,XXYY, 48,XXXY etc

93
Q

Outline features of kleinefelters

A
  • May present prenatally, during childhood with behavioural problems, or adulthood with infertility
  • Tall stature
  • Eunuchoid body habitus
  • Some behavioural and minor learning difficulties
  • Lack of secondary sexual characteristics – treat with testosterone
  • Infertility

Clinical Genetics (5 decks)

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