1AB, 2AB, 3AB Variants Flashcards
(87 cards)
1
Q
A couple has a child with cystic fibrosis(CF). All of the following statements are likely to apply to this family EXCEPT:
- prenatal diagnosis is available by DNA analysis
- for this couple the risk of having an affected child is 1 to 4
- heterozygotes are mildly affected with CF
- heterozygotes can be detected
A
- heterozygotes are mildly affected with CF
2
Q
What type of examination will you recommend to a 27-year-old woman pregnant for the first
time with no family history for malformations:
- examination of AFP
- amniocentesis
- biochemical prenatal screening for genetic diseases
- there is no need of examinations for genetic diseases
A
- biochemical prenatal screening for genetic diseases
3
Q
Which karyotype causes down syndrome:
- 47,XY.+18
- 46,XX,t(21;21)
- 45,XX,t(21;21)
- 45,XX,t(13;21)
A
- 46,XX,t(21;21)
OR
- 45,XX,t(13;21)
4
Q
Indicate the appropriate risk for abnormal child with phenylketonuria for a couple where the husband is genetically unaffected and the wife is affected by the same disease:
- 75%
- 25%
- 50%
- 0%
A
- 0%
5
Q
Karyotype 46,XXq - causes :
- klinefelter syndrome
- cri du Chat syndrome
- wolf-hirschorn syndrome
- turner syndrome
A
- turner syndrome
6
Q
Which aberration is balanced?
- inversion
- insertion
- deletion
- isochromosome
A
- inversion
7
Q
Which of the disease is NOT multifactorial
- cleft lip
- hunter syndrome
- anencephaly
- diaphragmatic hernia
A
- hunter syndrome
8
Q
Which statement is NOT true for Duchenne muscular dystrophy:
- X-recessive inheritance
- anticipatin
- is due to defective synthesis of the protein
- pseudohpertrophy of calf muscles is observed
A
- anticipatin
9
Q
What do turner syndrome and klinefelter syndrome have in common?
- short stature
- congenical heart defects
- intellectyal deficiency
- primary hypogonadism
A
- primary hypogonadism
10
Q
Which of the aberrations is polyploidy?
- 45,X
- 47XYY
- 48,XXXY
- 92,XXXX
A
- 92,XXXX
11
Q
Male has Azoospermia 186cm. which diagnose can be, which test?
OR
A proband appears with hypoplastic testes and azoospermia, and height of 186cm. What is the
most probable diagnosis and what kind of test would you perform to confirm it?
A
- Klinefelter Syndrome, which is diagnosed DURING / AFTER Puberty
- Karyotyping = 47, XXY
- Tests = Spermiogram, Blood Test (Shows DEPLETED Testosterone Levels)
NO Prenatal Screening Methods
12
Q
case (distal muscular trophy) Which diagnose? Which test?
A
Diagnosis = Distal Muscular Dystrophy
Test = Karyotyping, Blood Sampling, Check for Mutation (Multigenic)
Symptoms = Weakness in Lower Legs + Arms (Distal Muscles), spreading to other areas (Atrophy)
13
Q
picture ( turner syndrome) Seen symptoms in picture and 5 unseen symptoms
A
5 Seen Symptoms = 1. Neck Webbing 2. Hydrops 3. Short Stature 4. Wide-Spaced Nipples 5. Underdeveloped Breasts
5 Unseen Symptoms = 1. Infertility 2. Immature Uterus 3. Amenorrhea 4. High Blood Pressure
14
Q
(5) X-linked Recessive Criteria.
A
1) Mostly appears in MALES
2) IF man is affected => DAUGHTERS will be affected
3) Inheritance ONLY FROM Mother => SON
4) Unaffected Male CANNOT PASS gene due to 1 X Chromosome is NOT DEFECTIVE
5) 100% CHANCE the DAUGHTERS that have Unaffected MOTHER will HAVE the Disease!
15
Q
Distinguish Difference between X-recessive and Abdominal Dominant pedigree
A
X-Linked Recessive = ALMOST ALWAYS in MALE-MALE Transmission; Indirectly; SKIPS Generation
Abdominal Dominant = Males AND Females AFFECTED EQUALLY; EVERY Generation HAS it
16
Q
karyotype 21 only one chromosomes . 14 from 7 mark it
{Translocation BTW Chromosomes 14 + 21)
A
Down’s Syndrome
17
Q
NO family history. Give 3 sentences
{NO Family History, means X-Linked DOMINANT Conditions, so explain about that}
A
1) Autosomal Dominant
2) IF the FATHER is affected, ALL DAUGHTERS will be affected BUT NOT the Sons
3) IF it is FEMALE HETEROZYGOUS = 50% Affected ; IF FEMALE HOMOZOYGOUS = ALL CHILDREN are AFFECTED
18
Q
Haemophilia A - the X -linked criteria
A
1) X-Linked RECESSIVE
2) MAJORITY of MALES are AFFECTED, VIA the MOTHER (Carrier) OR (Affected w/ 2 R Alleles)
3) IF Affected is MALE = Father is GENETICALLY UNAFFECTED; Affected is FEMALE = Father is Healthy OR Affected
4) Males are MORE AFFECTED»_space; than Females
19
Q
Trisomy X . parents affected also risk in child
A
- Trisomy X is NOT INHERITED
- Due to RANDOM ERRORS (Non Disjunction IN MEIOSIS in 1 of the Parents)
- OR Due to MOSAIC FORM in Cell Division in Embryonic Development
- WOMEN with Trisomy X CAN have Children of their own
- Women who have a MIX of 46,XX (Typical F Karyotype) AND 47, XXX Cells = INCREASED RISK of Chromosomally ABNORMAL Children
20
Q
Wolf-hirschorn syndrome risk
A
- DUE to RANDOM Deletion in DISTAL Chromosome 4
- ~ 10% is INHERITED
- Autosomal DOMINANT
- Risk = 1 in 50, 000 Births
21
Q
What will you offer to a pregnant woman with low level of alpha-fetoprotein in maternal
serum?
A
- LOW Levels of AFP in Trisomy 18 & 21 {Down Syndrome}
- Karyotyping of Parents AND Foetus
- Amniocentesis
- Chorionic Villus Sampling
- Ultrasound
22
Q
Definition of ‘Expressivity’
A
The DEGREE of Expression of a PHENOTYPE, BY INDIVIDUALS with a SPECIFIC GENOTYPE
23
Q
Pedigree shows NO Family History. The Family has 3 Children AND 3 of them are Affected.
A
- Autosomal RECESSIVE
- NOT X or Y-Linked BECAUSE BOTH Males AND Females are AFFECTED!
- SKIPS Generation, hence RECESSIVE
24
Q
What is polyploid? 2 example disease?
A
- Where there’s MORE THAN 2 SETS of Chromosomes
(i) Trisomy
(ii) Tetraploidy
25
Point the mechanism that convert proto-oncogene to oncogene
DUE to Mutations that INCREASE Expression Level / Activity of Proto-Oncogene
- Point Mutations, Deletions OR Insertions that cause HYPERACTIVE Gene Product
- Point Mutations, Deletions OR Insertions in the PROMOTER REGION of the Proto-Oncogene, causing INCREASED Transcription
- Gene AMPLIFICATION, LEADING to EXTRA Chromosomal Copies of Proto-Oncogene
- Chromosomal TRANSLOCATION, CAUSING to RELOCATE Proto-Oncogene to a NEW Chromosomal Site, LEADING to a HIGHER Expression
- Chromosomal TRANSLOCATION, LEADING to a FUSION BETWEEN Proto-Oncogene AND a 2nd Gene (Produces a Fusion Protein with Oncogenic Activity)
26
5 indications for prenatal diagnosis?
1) Family History of Chromosomal ABNORMALITY
2) Family History of GENETIC DISORDER
3) ADVANCED Maternal Age (OLDER than 35 Y/o)
4) PREVIOUS Miscarriages / Stillbirths
5) PREVIOUS Infants WITH Birth Defects + HISTORY of NEURAL TUBE Defect
27
Explain the difference between variable expression AND incomplete penetrance.
Use at least 2 disease examples to illustrate your discussion
(4-5 sentences should be sufficient)
-Variable Expression = DEGREE of Expression of Phenotype, in DIFFERENT Individuals e.g. A POLYDACTYL Individual (Additional 2/3 Digits)
- Incomplete Penetrance = Likelihood that PHENOTYPE OCCURS DUE to SPECIFIC GENOTYPE e.g. BRCA1, BRCA2 (Breast Cancer Mutations)
28
2 individuals who both have achondroplasia mate.
What is the occurrence risk for this
disorder in their offspring?
- If they BOTH have Achondroplasia Mate, then ASSUME they are HETEROZYGOTES
- IF BOTH Heterozygote = 75% Affected, 25% Unaffected
- 1 Heterozygote, 1 Dominant Homozygote = 100% Affected
- BOTH Dominant Homozygotes = 100% Affected
29
Discuss the concept of pleiotropy.
Use at least 2 disease examples to illustrate the
concept.
(this answer should require no more than about 5 sentences.)
- Pleiotropy = Where 1 Gene AFFECTS 2 OR MORE Unrelated Phenotypic Traits
(i) Phenylketonuria = Gene CAUSES DEFICIENT Phenylalanine Hydroxylase, leading to INCREASED Phenylalanine Levels, AFFECTING NS + Heart
(ii) Marfan Syndrome = CT Disorder, AFFECTING Heart, Eyes + Blood Vessels
30
-Hereditary disease often present with NO previous family history of the disorder.
Briefly escribe 3 situations in which you would be most likely to observe a genetic disorder for which there is NO previous family history of the disease phenotype
(3 brief sentences should be sufficient)
1) De Novo Mutation
2) Uniparent Disomy
3) Gonadal Mosaicism / Germline Mutation
31
A man who is affected with Haemophilia A mates with a woman who is a heterozygous carrier of this disorder.
What proportion of this couple's daughters will be AFFECTED, AND what proportion of the daughters will be CARRIERS?
Haemophilia A, SO it is X-Linked RECESSIVE:
- 50% of Daughters will be AFFECTED
- 50% of Daughters will be CARRIERS
32
A Woman is coming to genetic counsellor with the following clinical features:
Difficulty releasing her hand after turning the door knob, distal muscle atrophy, and facial muscle weakness.
While taking her family history you discover the lost 2 babies shortly after birth because of respiratory insufficiency.
The woman's father also has ''muscle problems'' cataracts, and developed frontal
baldness at an early age.
You are Fairly Certain she has _______________
What Genetic Test will you recommend to Prove the Diagnosis? _____________________
- Fairly Certain she has MYOTONIC DYSTROPHY
- Genetic Test = Molecular Genetic Testing by doing a CTG Expansion IN the DMPK Gene
33
What is the TYPE of MUTATION which has been found in ALL patients with Huntington disease?
- Autosomal DOMINANT where a SINGLE GENE undergoes a REPEAT MUTATION of CAG Bases
34
Picture. Disease is KLİNFELTER SYNDROME . WRİTE AT LEAST 4 SYMPTOMS
- 47, XXY 48, XXXY - number of X chromosomes INCREASES,; SEVERITY of mental retardation &
malformation also INCREASES
- Infertile
- Tall with disproportionately long arms and legs
- Small testes
- Puberty occurs at normal age but facial hair growth is light
- IQ is 98 with mild decrease in verbal IQ
- Gynecomastia
35
The proband is a female with triple x syndrome.
What is the risk for her child to have the same
syndrome?
- Occurs due to a RANDOM GENETIC ERROR
- NOT Inherited, therefore NOT PASSED from Parent to Child = 0%
36
2 children of a young healthy couple are with Wolf-Hirschhorn syndrome.
What do you expect from 1 of the parents' karyotype?
- 46,XX, 4p- [del]
- BALANCED Chromosomal Translocation
37
What kind of genetic analysis will you offer to prove neurofibromatiss sign
- chromosomal analysis
- northern bloc
- southern blot
- westery blot
- chromosomal analysis
- southern blot **
- westery blot
38
Karyotype 46,XXi5p- causes:
- klinefelter syndrome
- Cri du chat syndrome
- Wolf -Hirscorp syndrome
- Turner syndrome
- Cri du chat syndrome
39
indicate the appropriate risk for abnormal child with cystic fibrosis is genetically unaffected and
the wife is a carrier
- 75%
- 50%
- 25%
- 0%
- 0%
40
Which one of the following combination of active an inactive x chromosome is 49,XXXXY individuals?
- 3 active and 1 inactive X chromosomes
- 0 active and 4 inacive x chrosomos
- 0 active inactive x chrosomes 4 active and 0 inactive X chrosomes
- 4 active and 6 inactive chrosomos
- 3 active and 1 inactive X chromosomes
41
According the morphologic characteristics human chromosomes are divided in EXCEPT
- metacentrics
- sub-metacentric
- acrocentries
- telocentrics
telocentrics
42
which karyotype causes down syndrome:
- 47,XY,+18
- 46,XX, t(13,21)
- 45,XX,t(21,21)
- 45,XX,t(13,21)
- 46,XX, t(13,21)
43
Which of the disease is multifactorial
- congenital adrenal hyperplasia
- Hunter sydrome
- Cleft lip
- pyleric stenosis
- Cleft lip
44
choose the symptom, which best characterizes down syndrome
- muscular hypotonia
- polidactyly
- mental retardation
- congenital hyperplasia
- mental retardation
45
The first genetic advice to a pregnant with thalassaemia minor is:
- amminoecentesis for excluding thalassaemia major
- cardocentesis for excluding thalassemia major
- examination of her partner for heterozygote carrier
- No examination is neccesary
- examination of her partner for heterozygote carrier
46
Which aberration is balanced?
- 46,XX,t(21,21)
- 46,XX,t(1,17)
- 46,XY,5p-
- 46,X
- 46,XX,t(21,21)
47
point at least 3 principles of genetic screening
1) disease is serious and relatively common -cost/benefit
2) natural history well defined
3) acceptable and effective treatment
4) prenatal diagnosis available for some conditions
48
What is the recurrent risk for patau's sydrome in a family with one child born with the syndrome and
karyotype 46,XY,t(13,13) parents are with normal karyotypes
- LESS than 1% = Since most cases are NOT inherited!
- CANNOT DETERMINE the EXACT risk SINCE the parents have a NORMAL Karyotype
49
1st child of a family is a boy. who has LESCH-NYHAN Syndrome
The fetus karyotype of their in preganancy is 46, XX.
What is the probability that this child would be with lesch- nyhan sydrome?
- 0%
- Karyotype is 46XX = girl - girls highly unlikely to affected unless the dad has X linked disease
- X-Linked Recessive therefore 25%
50
What will you recommend to a pregnant woman with Phenylketonurin?
- During Pregnancy, they should be on a Phenylalanine FREE Diet
51
What will you offer to a pregnant woman with HIGH level of alpha fetoprotein .
- HIGH Levels of AFP in Spina Bifida + Patau's Syndrome
- Ultrasound
- Surgery = Neurosurgery, Shunt, Plastic, Orthopaedic to correct limbs
52
Give Definition for nucleosome
- Consists of 8 histone proteins around
- which DNA wraps around 1.65 times.
53
Name at least 2features you would use to distinguish an
autosomal dominant pedigree AND X-linked dominant pedigree
- Autosomal Dominant = Males + Females are EQUALLY AFFECTED from Gen-to-Gen
- X-Linked Dominant = AFFECTED Males have AFFECTED Daughter; AFFECTS MORE Females >> Males
54
The proband is a male with karyotype 47,XYY. What is the risk for his child to have a syndrome?
- 50% chance of offspring to be trisomic with either 47XYY or 47XXY
- 50% chance to be normal
55
What genetic marker of chronic myeloid leukemia do you know?
- Philadelphia chromosome t[9:22]
- BCR/ABL gene
56
Point the mechanisms leading to loss of heterozygosity
Loss of 1 parent's contribution to the cell, DUE TO direct deletion, which is CAUSED BY
- unbalanced rearrangements
- gene conversion
- mitotic recombination
- loss of a chromosome (monsomy)
57
What is the most common mutation in the gene causing muscular dystrophy type Duchenne
- 60% Deletion
- 6% Duplication
LEADING to Frame Shift Mutation, producing Stop Codons + small Unstable Proteins LEADING to Absence / Reduced levels of DYSTROPHIN in Muscles
58
Point at least 5 indications for genetic counselling
- Person with family history of a known genetic disease
- Pregnant women with abnormal testing [fetal US/abnormal serum levels]
- Parents of children identified via newborn screening with abnormality
- Teratogenic exposure during pregnancy
- Couples with recurrent miscarriages/infertility
- Couples who are related
59
Describe dysmorphc features shown on the picture..........( the pictrure is Patau sydrome)
5 more sydrome
- Microcephaly [small head]
- Cleft lip/palate
- close set eyes
- mental retardation
- decreased muscle tone
- Extra fingers/toes [polydactyly],
- limb abnormalities, small eyes, small lower jaw
60
What pattern of inheritance does this picture most likely illustrate?
note that complication factors, such as reduced penetrance, may be present.
Assume that the gene frequency of the disorder in the general population is very low .
Give 3 examples.
- Autosomal Dominant Inheritance
1) Dominant Congenital Deafness
2) Dominant Deafness
3) Achondroplasia Dwarfism
1) Down Syndrome
2) Turner Syndrome
3) Cru Du Chat
61
What is the Difference between mitochondrial DNA AND Nulear DNA
- mtDNA = only contains information needed by mitochondria, DNA is circular & enclosed and NOT enveloped by membrane, inherited from mother, found only inside mitochondria
- Nuclear DNA = contains genetic info which codes to make the ENTIRE organism, present in nucleus of every cell, double helix structure linear open ended, enclosed by nuclear membrane
62
What is Sherman paradox ?
Term used to describe the anomalous pattern of inheritance found in FRAGILE X syndrome.
Aka ANTICIPATION or DYNAMIC MUTATION
63
What is the recuurent risk for Down syndrome in a family with
one child born with the same and karyotype 46,XY,t(15,21)
his mother's karyotype is 45,XX,t(15,21)
- 15%
64
the concepts of Anticipation .
Use at least 2 disease examples to illustrate the the concept
(should require no more than about 5 sentences)
- phenomenon where signs + symptoms of some genetic conditions tend to become more severe and/or appear at an earlier age
- as the disorder is passed from one generation to the next
65
What is the type of inheritance of beta thalassemia?
How many types of Beta thalassemia do u know?
Point at least 3 clinical symptoms of the disease?
- Autosomal recessive
- minor, intermediate, major
- Symptoms = paleness, growth retardation due to severe anemia, bone deformities & hepato-splenomegaly develops later on
66
point at least 3 principles of genetic screening
1) Disease
- It's Serious & Common
- Natural history WELL-DEFINED
- ACCEPTABLE + EFFECTIVE Tx
- Prenatal Diagnosis
2) Test
- INexpensive
- Valid + Reliable
- Easy to PERFORM
- SOCIALLY Acceptable
3) System
- RESOURCES for Diagnosis / Tx are ACCESSIBLE
- Results are Communicated EFFECTIVELY + EFFICIENTLY
67
penetrance is:
- measurement for the length of the chromosome
- frequency of expression of a phenotype among homozygotes of AR gens
- frequency of expression of a phenotype among heterozygotes of AD gens
- Type of gene mutation
- frequency of expression of a phenotype among heterozygotes of AD gens
68
Karyotype 47,XXY causes:
- Klinefelter syndrome
- Cri du chat sndrome
- wolf honshorn sydrome
- Turner sydrom
- Klinefelter syndrome
69
For multifactorial type of inheritance is characterized:
- lower risk when parents are relatives
- the risk of recurence is 25%
- genes contralling trac ac additivly
- the recurrent risk depends on mothoer's genotype
- genes contralling trac ac additivly
70
Myotonic dystrophy inheritance is :
- autosomal dominant
- X-recessive
- X-dominant
- multifactorial
- autosomal dominant
71
Choose the BALANCED karyotype:
- 46,XrX
- 46,XY,5p-
- 46,XY,t(3, 12)
- 46,XY,t(13, 14)
- 46,XY,t(13, 14)
72
Which of disease is X - linked Recessive
- morris syndrome
- Hurler syndrome
- cystic fibrosis
- congenital adrenal hyperplasia
- morris syndrome
73
İndicate the appropriate risk for a child with sickle cell anemia of a couple where the husband is genetically unaffected and the wife is a carrier
- 75%
- 50%
- 25%
- 0%
- 0%
73
Which of the disease is NOT multifactorial
- congenital adrenal hyperplasia
- congenital heart disease
- diaphragmatic hernia
- schizophrenia
- congenital adrenal hyperplasia
74
Give definition for sex chromatin
when during the cell cycle you will see it.
How many types of sex chromatin do you know?
- Sex Chromatin = Females have 2x Chromosomes where 1 is Active, and other is Inactive - found in Somatic Cells
- Seen in INTERPHASE of Cell Cycle
- 2 Types = X and Y
75
Point three clinical symptoms of cooley's anamia and how it is inherited.
- Hepatosplenomegaly
- Anaemia
- Growth Retardation
- Bone Derformities
76
A woman with an X-linked dominant disorder mates with
a phenotypically normal male average.
what proportion of this couple's daughters will be affected with the disorder?
Mother is HETEROZYGOUS = 50%
IF HOMOZYGOUS = ALL of her Children
77
1st child of a family is a boy. who has HUNTER SYNDROME
The fetus karyotype of their in pregnancy is 46, XX.
What is the probability that this child would be with Hunter Syndrome?
- 25% Hunter
- X-Linked RECESSIVE = Females are CARRIERS, so NOT Affected
78
A phenotypically normal couple with negative family history produces four children, have MARFAN SYNDROME
What is the most likely explanation for this?
- De Novo Mutation
79
Pİctures ( down sydrome ) 5 more symptoms
- Mental Retardation
- Congenital Heart Disease
- Enlarged Colon
- Hypotonia
- Stubby Fingers
80
Explain the concept of IMPRINTING.
Use disease examples to illustrate your points?
- Imprinting = A Parental EFFECT on GENE Expression
E.g. PRADAR-WILLI Syndrome
81
what is the risk for a child with chromosomopathy of a man with karyotype 46,XYY?
- 50%
82
What genetic marker of Burkitt lymphoma do you know?
- C myc Gene
83
What is the recurrent risk for Edwards's syndrome in a family with one child born with the same syndrome and normal karyotypes of the patients?
What will you recommend during the pregnancy?
- 1% Risk
- Recommend Prenatal Diagnosis
84
Which is the parameter in maternal serum for detecting Down syndrome in the first or second
trimester?
- 1st Trimester = CG + PAPP INCREASE
- 2nd trimester - AFP + UE3 DECREASE
85
What is the different between mitochondrial DNA and nulear DNA?
- Mitochondrial DNA = Found in Mitochondria; Each Mito has SEVERAL Copies of mtDNA; Maternal Only; Free of Nuclear Envelope; DNA iS NOT packed into Chromatin
- Nuclear DNA = In Nucleus; 2 sets of 23 Chromosomes; Maternal + Paternal; Double Helix: Packed into Chromatin W/ Nuclear Envelope
86
What is the most common mutation in the gene causing muscular dystrophy type
Becker?
Point Mutation
