Genetics

Question 1

How is the distribution of chromosomal abnormalities in spermatozoa and mature oocyte?

Answer 1

10% in spermatozoa and 25% in mature oocyte.

And are common cause of early spontanous miscarriage.

Question 2

What is the most common autosomal trisomy and genetic cause of severe learning difficulties?

Answer 2

Down syndrome

Question 3

what are the clinical features of Down syndrome?

Answer 3

hypotonic, flat occiput, single palmar creases, incurved fifth finger, and wide sandal gap between the big and second toes.
Check others

Question 4

What should you do before taking blood sample of a suspected down syndrome baby?

Answer 4

INFORM THE PATIENT

Question 5

How long time may it take to get the results of real-time PCR or rapid fluorescence in sidu hybridization technique in case of Down syndrome?

Answer 5

1-2 days

Question 6

What is the 1-year prognosis of down syndrome?

Answer 6

85%

Question 7

what is the major cause of mortality in DS?

Answer 7

Congenital heart defects which is present in about 40%, particularly atrioventricular defects

Question 8

Other than congenita heart diseas, what other abnormality is common in DS at newborn period?

Answer 8

duedenal atresia

Question 9

The extra chromosome 21 may result from what kind of genetic default?

Answer 9

Meiotic nondisjunction (94%), translocation or mosaicism.

Question 10

What is the mechanism of nondisjunction trisomy 21 and what is it related to?

Answer 10

• most cases result from an error at meiosis
• the chromosome 21 fails to separate, so that one gamate has two chromosome 21s and one has none.
• fertilization of the gamate with two chromosme 21s gives rise to a zygote with trisomy 21
• parental chromosomes do not need to be examined
• related to maternal age

Question 11

What is the mechanism of translocation?

Answer 11

when extra chromoseome 21 is joined onto another chromosome (usually chromosome 14, but occasionally chromosome 15, 22, or 21), this is known as a Robertsonian translocation.

Question 12

What is the characteristic of mosaisism?

Answer 12

some cells are normal and some have trisomy 21.

Question 13

Which disease is trisomy 13 and 18?

Answer 13

Edwards (18) and patau (13)

Question 14

What diagnostic tools is used to diagnose trisomy 13 and 18?

Answer 14

Chromosomal analysis, ultrasound (usually in second trimester), amniocentesis, and non-invasive prenatal testing (NIPT).

Question 15

What are the clinical features of Edwards syndrome (18)?

Answer 15

Low birthweight, prominent occiput, small mouth and chin, short sternum, flexed overlapping fingers, Rocker-bottom feet, cardiac and renal malformations.

Question 16

What are the clinical features of Patau syndrome (13)?

Answer 16

Structural defect of brain, scalp defects, small eyes (microphtalmia) and other eye defects, cleft lip and palate, polydactyly, cardiac and renal malformations.

Question 17

How common is early miscarriage in Turner syndrome (45, X)?

Answer 17

95%

Question 18

Turner syndrome can be detected antenatally on ultrasound, what do we see?

Answer 18

fetal edema of the neck, hands, or feet or a cystic hygroma may be identified.

Question 19

What are the clinical features of Turner syndrome?

Answer 19

lymphedema of hands and feet in neonate, which may persist.
spoon-shaped nails, short stature, neck webbing or thick neck.
wide carrying angle (cubitus valgus), widely spaced nipples, congenital heart defects (particularly coarctationof the aorta),
Delayed puberty, ovarian dysgenesis resulting in infertility, although pregnancy may be possible with in vitro fertilization using donated ova.
hypothyroidism, renal anomalies, pigmented moles, recurrent otitis media, and normal intellectual function in most cases.

Question 20

Whats the percentage of turner syndrome individuals that have 45 chromosome with only one X chromosome?

Answer 20

50%

Question 21

The presence of y chromosome may increase the risk of what cancer?

Answer 21

Gonadoblastoma

Question 22

What is reciprocal translocations?

Answer 22

an exhange of material between two different chromosomes

Question 23

what is balanced reciprocal translocation and unbalanced?

Answer 23

when exchange involves no loss or gain of chromosome material, the translocation is balanced and is not phenotypic.
unbalanced is when there is an incorrect amount of chromosomal material and often impaire both physical and cognitive development, leading to dysmorphic features, congenital malformations, developmental delay, and learning difficulties.

Question 24

What is Mendelian inheritance? give an example

Answer 24

it is the transmission of inherited traits or diseases caused by variation in a single gene in a characteristic pattern.
Autosomal dominant inheritance is an example and most common. Caused by alterations in only one copy of a gene pair.

Question 25

List examples of autosomal dominat disorders

Answer 25

achondroplasia, Ehlers-Danlos syndrome, familial hypercholesterolemia, Huntington disease, Marfan syndrome, Myotonic dystrophy, Neurofibromatosis, Osteogenesis imperfecta, and polyposis coli.

Question 26

Give an example of a delition disease

Answer 26

Cri-du-chat syndrome, DiGeorge syndrome and Williams syndrome

Question 27

give an example of a duplication disease?

Answer 27

Charcot-Marie-Tooth disease

Question 28

Tell about X-linked inheritance

Answer 28

Caused by alterations in genes of X chromosomes.

• males are affected
• female carriers are usually healhty
• occasionally a female carrier shows features of the disease
• each son of a female carrier has 50% risk of being affected
• each daughter of a female carrier has a 50% risk of being a carrier
• daughters of affected males will all be carriers
• sons of affected males will not be affected, because a man passes a Y chromosome to his sons.

Question 29

In X-linked dominant disorders, how is male and female affected?

Answer 29

female carrying the mutation will be affected while male carrying the mutation will have more serious condition.

Question 30

Examples of X-linked recessive disorders:

Answer 30

• Colour blindness (red-green)
• Duchenne and Becker muscular dystrophy
• Glucose-6-phosphate dehydrogenase
• Hemophilia A and B
• Hunter syndrome (mucopolysaccharidosis II)

Question 31

examples of autosomal recessive disorders:

Answer 31

• Galactosemia
• glycogen storage disease
• cystic fibrosis
• fridreich ataxia
• congenital adrenal hyperplasia
• phenylketouria
• Tay-sach disease
• Sickle cell disease
• Thalasemia

Question 32

What is trinucleotide repeat expansion mutation?

Answer 32

a kind of mutation in which repeats of three nucleotides (trinucleotide repeats) increase in copy numbers until they cross a threshold above which they become unstable.

Question 33

Give example of trinucleotide repeat expansion:

Answer 33

Huntington disease, Fragile X syndrome and myotonic dystrophy.

Question 34

Explain the two catagories of triplet repeat disorders:

Answer 34

1: when triplet repeat expansion is in the coding sequence (Huntington), proteins containing an excess of the amino acid, glutamin are produced.
2: when triplet expansion is in other regions of the gene, reduced quantities of the protein are produced. In these cases, the reduction in the amount of the avilable protein leads to the symptoms of the condition.

Question 35

Most triplet repeat are autosomal domina, but one is autosomal recessive and another is X linked, which?

Answer 35

Friedreich ataxia is autosomal reccesive and Fragile X syndrome is X linked.

Question 36

How to diagnose Fragile X syndrome?

Answer 36

molecular analysis of trinucleotide repeat expansion in the relevant gene

Question 37

Does fragile X syndrome cause any learning difficulties in women?

Answer 37

even tho it is x linked, 40-50% of women have learning difficulties (mild-moderate).

Question 38

Usually in X linked disorders, male cannot inherit the condition from his family and transmit the condition to his children without himself being affected, how is it in Fragile X?

Answer 38

this can occur because the triplet repeat expansion varies in its nature with its size.

Question 39

What is the most common genetic cause of severe learning difficulties?

Answer 39

Down syndrome

and Fragile X syndrom is SECOND most common.

Question 40

Clinical features in males in Fragile X syndrome:

Answer 40

• moderate-severe learnign difficulties (IQ 20-80, mean 50).
• Macrocephaly
• Macroorchidism-postpubertal
• face: long, face, large everted ears, prominent mandible, and broad forehead, most evident in affected adults
• Other: mitral valve prolapse, joint laxity (loose joints), scoliosis, autism, hyperactivity

Question 41

What is imprinting? and give example of a disease

Answer 41

Imprinting is the unusual property of some genes that express only the copy derived from the parent of a given sex.
Two syndromes are derived from mutatino of same area of the chromosome but are different in who got the mutation
- Prader-Willi- syndrome (from paternal chromosomal region, hypotonia, developmental delay, hyperphagia, and obesity)
- Angelman syndrome from same region but on maternal (severe cognitive impairment, characteristic facial appearance, ataxia, epilepsy because of a lack of expression of the UBE3A gene and the paternal coby bein imprinted.