GENETICS IN CLINICAL OBSTETRICS AND GYNAECOLOGY Flashcards
1
Q
Genomics
A
- preconceptional and prenatal testing
- Newborn screening
- Disease susceptibility
- Screening and diagnosis
- Prognosis and therapeutic decision
- Monitoring disease burden and recurrence
2
Q
a stretch of nucleotides that code for a
polypeptide
A
gene
3
Q
code for the protein that
the gene encodes
A
Exons
4
Q
Codons
A
- Is genetic code
- made of RNA
- Consists of 3 sequential nucleotides
- Total possible number of codons is 64
(because DNA contains 4 nucleotides) - Is degenerate (ie. more than 1 codon
can specify the same amino acid but no
codon specifies more than 1 amino acid)
5
Q
types of chromosomes
A
i. Metacentric (i.e. the 2 arms of the chromosome are equal in length)
il. Submetacentric
iii Acrocentric
iv. Telocentric (do not exist in humans)
v. Holocentric (do not exist in humans)
6
Q
Largest chromosome
A
chromosome 1
7
Q
Smallest chromosome
A
chromosome 22
8
Q
Colchicine inhibits spindle formation. T/F
A
T
9
Q
EDTA inhibits deoxyribonuclease. T/F
A
T
10
Q
at metaphase, chromosome is identified by — stain
A
Giemsa stain
11
Q
Genetic diseases can be categorized into
three major groups:
A
- chromosomal disorders
- single gene (monogenic) disorders
- multifactorial disorders
12
Q
chromosomal abnormalities are subclassified into 2:
A
- numerical
- structural
13
Q
numerical chromosomal abnormalities are - and -
A
- aneuploidy
- polyploidy
14
Q
the six structural chromosomal abnormalitites are:
A
- translocation
2 deletion - insertion
- inversion
- rings
- isochromosome
15
Q
*Aneuploidy refers to
A
an extra or missing chromosome, such as
–in trisomy 21 (Down syndrome) or
–monosomy 45XO (Turner syndrome)
16
Q
Polyploidy refers to
A
numerical chromosome abnormalities in which
there is an addition of an entire complement of haploid chromosomes,
such as in
–triploidy, in which three haploid sets occur (69, XXX or XXY or XYY).
–Tetraploidy-4 haploid sets occuring
17
Q
Numerical or aneuploid chromosome abnormalities involve either
autosomes or sex chromosomes. T/F
A
T
18
Q
Most numerical chromosome abnormalities occur as the result of nondisjunction during meiosis or mitosis in which homologous chromosome pairs fail to disjoin. T/F
A
T
19
Q
Nondisjunction occurs most commonly at meiosis 2. T/F
A
F. meiosis 1
20
Q
there a strong correlation between increasing
maternal age and incidence of nondisjunction. T/F
A
T
21
Q
Down syndrome has 3 copies of chromosome 21. T/F
A
T
22
Q
——–% of down syndrome are caused by nondisjunction at gametogenesis
A
95%
23
Q
—–% are mosaic for trisomy21
A
1–3%
24
Q
—-% of individuals with clinical Down syndrome have a structural rearrangement (Robertsonian translocation)
A
2–4%
25
incidence of down syndrome
1:800
26
incidence of edward's syndrome
1: 6000
27
incidence of Patau syndrome
1:15,000
28
incidence of turner syndrome
1:5000
29
incidence of klinefelter syndrome
!:1000
30
incidence of triple x syndrome
!:1000
31
incidence of xyy syndrome
1:1000
32
T/F: In human genetics only aberrations arising within germ cells are important
T
33
Examples of Diseases from deletions
*Cri-du-chat(5p-) syndrome
*DiGeorges Syndrome
*Wilms tomour
*Angelman and Prader-Willis yndrome
34
chromosome loses a segment because of breakage
deletion
35
rearrangements of the gene order within a single chromosome due to the incorrect repair of two
breaks
Inversion
36
centromere is outside inverted region
Paracentric inversion
37
centromere is within the inverted region
Pericentric inversion
38
the exchange of chromosomal material between two nonhomologous chromosomes
Translocation
39
2 types of translocation
1. balanced reciprocal translocation
2. robertsonian translocation
40
T/F: Balanced Reciprocal Translocations occur as a result of a mutual and physical exchange of chromosome (genetic) material between homologous chromosomes
F. non homologous chromosomes
41
T/F: Balanced Reciprocal Translocations cause no problem for mitosis
T
42
T/F: Balanced Reciprocal Translocations cause no problem for meiosis
F: may result in unequal distribution of chromosomes
43
incidence of balanced reciprocal translocations
1/11,000
44
T/F: The carrier of a reciprocal balanced translocation is usually phenotypically normal
T
45
T/F: balanced reciprocal translocation is associated with advanced paternal age
T
46
Involves any two acrocentric chromosomes that break near the
centromeres and re-join in a way that results in the long arms(q arms)
fusing at the centromere, forming a single chromosome structure and
loss of the short arms( p arm)
Robertsonian translocation
47
incidence of robertsonian translocation
1/9000 pregnancies
48
T/F: An individual with robertsonian translocation is genetically balanced, that is, he or she has two copies of each chromosome
T
49
T/F: The gametes in robertsonian translocation are balanced
F.
the gametes are at risk to be unbalanced
50
----% of Down syndrome have Robertsonian translocation
5%
51
major congenital abnormality in robertsonian translocation is seen in ---%
4%
52
T/F: numerical abnormalities are not inherited
T. Occur as random events during formation of reproductive cells
53
T/F: some structural abnormalities are inherited
T. some also occur as random events during formation of reproductive cells or early fetal development
54
T/F: single gene disorders or mendelian inheritance
T
55
incidence of single gene disorders
3.6/1000 live births (2% of population)
56
the probability that a gene will have any phenotypic expression at all
Penetrance
57
the degree to which the phenotype is expressed
Expressivity
58
Five basic modes of inheritance for Single-gene
diseases
–Autosomal dominant
–Autosomal recessive
–X-linked dominant
–X-linked recessive
–Mitochondria
59
in autosomal dominant inheritance affected individuals have a -------% chance of
transmitting the gene
50% (Inheritance =1:2)
60
The gene product in autosomal dominant inheritance is commonly ----
non-enzymatic protein
61
T/F: Autosomal Recessive inheritance is not typically seen in every generation
(NOT possible to trace via Family tree)
T
62
T/F: females are more affected than males in autosomal recessive diseases
F. Males and female equally affected
63
T/F: Consanguinity increases risk of offspring
T
64
The gene product in autosomal recessive inheritance is commonly -----
an enzyme
65
T/F: incidence of X-linked recessive disorders is seen only in males
F. much higher in males than females
66
T/F: there's no father to son transmission in xlinked recessive disorders
T
67
----% of daughters of affected males are carriers
100%
68
what is the % of inheritance in son and daughters of carrier females
50% of sons infected and 50% of daughters carriers
69
X-linked dominant disorders are seen in only females
F.
males and females affected but females more severely affected
70
for an affected male in X-linked dominant inheritance, what is the incident of transmission to his sons and daughters?
no male to male transmission
all daughters affected
71
in X-linked dominant disorders, for an affected female what is the incidence of transmission to sons and daughters
1 in 2 risk to children (M+F)
72
T/F: In mitochondrial inheritance it is difficult to determine the risk of transmission to offspring
T
73
T/F: All genes in multifactorial diseases work in the context of environment and behavior
T
74
T/F: Only single disorders follow a clearly defined pedigree pattern of inheritance “Mendelian Pattern”.
T
75
T/F: In Mendelian Inheritance, for several diseases the family tree may be conclusive even if accurate diagnosis is not made
T
76
Essential Components of Genetic Counselling
1. History and pedigree construction
2. Clinical Examination
3. Confirmatory diagnosis
4. Calculation of recurrence risk
5. Counselling
6. Follow-up
77
ETHICAL PRINCIPLES
1. Beneficence
2. Autonomy
3. Justice
4. Non-Maleficence
5. Veracity
6. Fidelity
78
maternal serum screening for prenatal diagnosis
fetoprotein, estriol and hcg estimation
79
amniocentesis for prenatal diagnosis
fetoprotein, acetylcholinesterase, chromosomal analysis, biochemical analysis
80
CVS for prenatal diagnosis
chromosomal analysis, biochemical analysis, DNA analysis
81
Fetal blood sampling for prenatal diagnosis
chromosomal analysis, DNA analysis
82
Invasive methods of prenatal diagnosis
1. coelocentesis
2. CVS
3. Amniocentesis
4. cordocentesis
5. biopsy from fetal tissue
83
Non invasive methos of prenatal diagnosis
1. cell free fetal DNA
2. triple test
3. USS
4. MRI
84
amniocentesis is performed in which trimester
2nd
85
incidence of miscarriage with amniocentesis
1 in 300 - 500
86
CVS is done in which trimester
2nd
87
risk of miscarriage with CVS
1 in 300 -500
88
cordocentesis is also called
PUBS
89
when can cordocentesis be done
after 18 weeks
90
what is the risk of miscarriage with cordocentesis
2 in 100 women will miscarry
91
at what GA should fetal tissue biopsy be done
17 - 20 weeks
92
T/F: < 1 in 1000 women will get infection with fetal tissue biopsy
T
93
at what GA should coelocentesis be done
before 10 weeks
94
the space between the amniotic cavity and uterine cavity
coelomic space
95
incidence of fetal loss with coelocentesis
0 or < seen in amniocentesis
96
fetal fraction in maternal blood for cell-free fetal DNA
>3.5%
97
T/F: cell-free fetal DNA is affected by gestational age and maternal BMI
T
98
T/F: High false positive rates with cell-free fetal DNA
F. low
99
reason for false positives seen with cell-free fetal DNA testing
results confounded by placental mosaicism, chromosomal translocations, uniparental disomy, vanishing twin
100
T/F: cell-free fetal DNA can detect trisomies 18, 13 and 21
T
101
triple test meases --,--- and --
alpha fetoprotein, hcg and unconjugated estriol
102
quadruple test measures --,--,-- and --
alpha fetoprotein, hcg, unconjugated estriol and inhibin A
103
T/F: adequate DNA is obtained with one process of PCR examination
F.
Repeat process 30 times to get adequate DNA
104
T/F: PCR identify specific DNA sequence for gene mutation & prenatal Dx.
at an earlier stage before an embryo transfer in IVF cycle.
T
105
FISH detects specific DNA sequences in -- and-- phases of the cell cycle
interphase and metaphase.
106
T/F: FISH results are available in one week
F. 24-48hrs
107
T/F: FISH allows detection of big structural rearrangements
F.
108
FISH Identifies ---% clinically relevant abnormalities
80%
109
read the order of bases (ATGC) in genome of an individual
sequencing
110
first generation sequencing
sanger sequencing: single gene disorders, 300-1000bp, cost implication
111
second generation sequencing
1. pyrosequencing:
2. ion torrent
3. illumina sequencing
112
3rd generation sequencing
pacific biosciences: single molecule real time sequencing, epigenetic studies
113
4th generation sequencing
nanopore technology
114
ADVANTAGES OF next generation sequencing
1. targeted gene sequencing
2. whole genome sequencing: entire nucleotide sequence of the genome
3. whole exome/clinical exome sequencing: protein coding regions
115
examples of multifactorial diseases
Spina bifida, diabetes, and heart disease
116
examples of X linked dominant diseases
FAIR:
F - (oro) facial syndrome
A - alports
I - incontinenta pigmento
R - resistant rickes (hypophosphatemic)
R - Rett syndrome
117
examples of X-linked recessive diseases
(Be Wise, Fools GOLD Heeds Silly Hope)
B - Bruton's agammaglobulinaemia
W - Wilscot aldrich syndrome
F - Fabry's syndrome
G - G6PD deficiency
O - ocular albinism
L- lesch nyhan syndrome
D - dystrophy (duchenne's and beckers)
H - hunter's syndrome
H - haemophilia A and B
118
examples of autosomal recessive diseases
PASTA CHAWAL
P - phenylketonuria
A - alkaptonuria
S - sickle cell anaemia
Ta - thalasemia
C - cystic fibrosis
H - haemochromatosis
A - alpha AT deficiency
W - wilson disease
A- albinism, adrenal hyperplasia
L - lysosomal and glycogen storage disease
119
examples of autosomal dominant diseases
Very Powerful DOMINANT Humans
V - von willebrand and von hippel lindau
P - pseudohypoparathyroidism
D - dystrophia myotonica
O - osteogenesis imperfecta and osler weber rendu
M - marfan syndrome
I - intermittent porphyria
N - neurofibromatosis
A - achondroplasia and adult polycystic kidney disease
N - noonan syndrome
T - tuberous sclerosis
H - hypercholesterolaemia, huntington disease, hypertrophic obstructive cardiomyopathy, hereditary spherocytosis, hereditary non polyposis colon ca, hereditary haemorrhagic telangiectasia
