Complex Multigenic and Cytogenetic Disorders MCQs

Question 1

What is the minimum population frequency required for a genetic variant to be classified as a polymorphism?

Accepted Answer

10% — A polymorphism is defined as a genetic variant that has at least two alleles and occurs in at least 1% of the population.

Question 2

In complex multigenic disorders, what percentage of type 1 diabetes risk is contributed by a few HLA alleles?

Accepted Answer

More than 50% — Of the 20 to 30 genes implicated in type 1 diabetes, a few HLA alleles contribute more than 50% of the risk.

Question 3

Which environmental factor is most commonly associated with unmasking the genetic trait in type 2 diabetes mellitus?

Accepted Answer

Obesity — Type 2 diabetes often first manifests clinically after weight gain, demonstrating how obesity as an environmental factor unmasks the genetic trait.

Question 4

What proportion of newborn infants has some form of chromosomal abnormality?

Accepted Answer

1 in 200 — It is estimated that approximately 1 in 200 newborn infants has some form of chromosomal abnormality.

Question 5

What percentage of first-trimester spontaneous abortions are associated with chromosomal abnormalities?

Accepted Answer

50% — Approximately 50% of first-trimester spontaneous abortions are associated with chromosomal abnormalities.

Question 6

Which staining technique is widely used to produce distinctive banding patterns on chromosomes?

Accepted Answer

Giemsa stain (G banding) — The Giemsa stain (G banding) technique produces a distinctive pattern of alternating light and dark bands allowing identification of each chromosome.

Question 7

A chromosome number of 3n is classified as:

Accepted Answer

Polyploid — Any exact multiple of the haploid number (n) is called euploid; numbers such as 3n and 4n are specifically called polyploid.

Question 8

What is the primary cause of aneuploidy?

Accepted Answer

Nondisjunction during meiosis — The chief cause of aneuploidy is nondisjunction of a homologous pair of chromosomes at the first meiotic division or failure of sister chromatids to separate during the second meiotic division.

Question 9

What is the chromosome count in a trisomic zygote?

Accepted Answer

2n – 1 — When a gamete with an extra chromosome (n + 1) is fertilized by a normal gamete (n), the resulting zygote is trisomic (2n + 1).

Question 10

Which type of chromosomal abnormality is better tolerated: autosomal or sex chromosomal?

Accepted Answer

Sex chromosome imbalances — Imbalances of sex chromosomes are tolerated much better than similar imbalances of autosomes. ### SECTION B: CHROMOSOMAL TERMINOLOGY & NOTATION

Question 11

What does mosaicism refer to in cytogenetics?

Accepted Answer

Presence of two or more cell populations with different chromosome complements — Mosaicism is the presence of two or more populations of cells with different complements of chromosomes in the same individual.

Question 12

In cytogenetic notation, what does "p" represent?

Accepted Answer

Short arm (petit) — "p" (French, petit) denotes the short arm of a chromosome; "q" denotes the long arm.

Question 13

What does the notation 46,XX,t(2;5)(q31;p14) indicate?

Accepted Answer

Reciprocal translocation between chromosomes 2 and 5 — This notation indicates a reciprocal translocation involving the long arm of chromosome 2 and the short arm of chromosome 5.

Question 14

What is a Robertsonian translocation?

Accepted Answer

Translocation between two acrocentric chromosomes — Robertsonian translocation is a reciprocal translocation between two acrocentric chromosomes involving the short arm of one and long arm of the other.

Question 15

What is the most common isochromosome found in live births?

Accepted Answer

i(Xq) — The most common isochromosome in live births involves the long arm of the X chromosome, designated i(Xq).

Question 16

How does an isochromosome form?

Accepted Answer

Horizontal division of centromere — Isochromosomes result when the centromere divides horizontally rather than vertically, leading to loss of one arm and duplication of the other. ### SECTION C: DOWN SYNDROME (TRISOMY 21)

Question 17

What percentage of Down syndrome cases are caused by trisomy 21?

Accepted Answer

95% — About 95% of affected persons with Down syndrome have trisomy 21 (chromosome count of 47).

Question 18

What is the maternal age-related incidence of Down syndrome in women older than 45 years?

Accepted Answer

1 in 25 — Incidence increases dramatically to 1 in 25 live births in women older than 45 years.

Question 19

In what percentage of Down syndrome cases is the extra chromosome of maternal origin?

Accepted Answer

95% — In 95% of cases, the extra chromosome is of maternal origin, indicating meiotic nondisjunction primarily in the ovum.

Question 20

What percentage of Down syndrome cases result from translocation?

Accepted Answer

15% — In about 4% of patients, the extra chromosomal material is present as a translocation of the long arm of chromosome 21 to chromosome 22 or 14.

Question 21

What percentage of Down syndrome patients are mosaics?

Accepted Answer

10% — Approximately 1% of patients are mosaics, having a mixture of 46- and 47-chromosome cells.

Question 22

What percentage of Down syndrome patients have congenital heart disease?

Accepted Answer

40% — Approximately 40% of Down syndrome patients have congenital heart disease, most commonly endocardial cushion defects.

Question 23

What is the increased risk of acute leukemia in children with Down syndrome?

Accepted Answer

10- to 20-fold — Children with trisomy 21 have a 10- to 20-fold increased risk of developing acute leukemia.

Question 24

At what age do virtually all Down syndrome patients develop neuropathologic changes characteristic of Alzheimer disease?

Accepted Answer

Over age 40 — Virtually all patients with trisomy 21 older than age 40 develop Alzheimer-like neuropathologic changes.

Question 25

What is the current median age at death for persons with Down syndrome?

Accepted Answer

47 years — Improved medical care has increased longevity, with the current median age at death being 47 years.

Question 26

Which immune cell function is primarily affected in Down syndrome patients?

Accepted Answer

T cell functions — Patients demonstrate abnormal immune responses affecting mainly T cell functions, predisposing them to infections.

Question 27

What is the typical IQ range for approximately 80% of individuals with Down syndrome?

Accepted Answer

25 to 50 — Approximately 80% of those afflicted have an IQ of 25 to 50. ### SECTION D: OTHER AUTOSOMAL DISORDERS

Question 28

Which deletion syndrome results from partial deletion of the short arm of chromosome 5?

Accepted Answer

Cri du chat syndrome — Cri du chat syndrome results from partial deletion of the short arm of chromosome 5 (5p-).

Question 29

What is the chromosomal abnormality in Patau syndrome?

Accepted Answer

Trisomy 13 — Patau syndrome is caused by trisomy 13.

Question 30

What is the chromosomal abnormality in Edwards syndrome?

Accepted Answer

Trisomy 18 — Edwards syndrome is caused by trisomy 18. ### SECTION E: 22q11.2 DELETION SYNDROME

Question 31

Which chromosome is involved in 22q11.2 deletion syndrome?

Accepted Answer

Chromosome 22 — The syndrome results from a small interstitial deletion on the long arm of chromosome 22.

Question 32

Which two previously separate syndromes are now known to be caused by 22q11.2 deletion?

Accepted Answer

DiGeorge and velocardiofacial syndromes — DiGeorge syndrome and velocardiofacial syndrome are both caused by 22q11.2 deletion.

Question 33

Which transcription factor gene is suspected to be responsible for 22q11.2 deletion syndrome?

Accepted Answer

TBX1 — The transcription factor gene TBX1 is suspected to be responsible for the clinical features.

Question 34

What diagnostic technique is used to establish the diagnosis of 22q11.2 deletion syndrome?

Accepted Answer

Fluorescence in situ hybridization (FISH) — Diagnosis is established by detecting the deletion using FISH.

Question 35

Which type of immunity is impaired in DiGeorge syndrome?

Accepted Answer

T cell immunity — DiGeorge syndrome features thymic hypoplasia with impaired T cell immunity.

Question 36

What metabolic abnormality is commonly seen in DiGeorge syndrome due to parathyroid hypoplasia?

Accepted Answer

Hypocalcemia — Parathyroid hypoplasia results in hypocalcemia. ### SECTION F: COMPLEX INHERITANCE & GENETIC CONCEPTS

Question 37

According to the common disease-common variant hypothesis, complex multigenic disorders occur when:

Accepted Answer

Many polymorphisms with modest effects are co-inherited — Complex disorders occur when many polymorphisms, each with a modest effect, are co-inherited.

Question 38

How many genes are most important among the 20 to 30 genes implicated in type 1 diabetes?

Accepted Answer

6 to 7 — Of the 20 to 30 genes implicated, 6 or 7 are considered most important.

Question 39

What does QTL stand for in genetics?

Accepted Answer

Quantitative trait loci — Quantitative trait loci (QTLs) govern multigenic inheritance showing continuous variation (e.g., height).

Question 40

In general, which produces more severe defects?

Accepted Answer

Loss of chromosomal material — Loss of chromosomal material (deletion, monosomy) generally produces more severe defects than gain (trisomy).

Question 41

What is the outcome of polyploidy in most cases?

Accepted Answer

Spontaneous abortion — Polyploidy (3n, 4n) generally results in spontaneous abortion.

Question 42

Which type of mosaicism is more common?

Accepted Answer

Sex chromosome mosaicism — Mosaicism affecting sex chromosomes is common; autosomal mosaicism is rare.

Question 43

What is the result of anaphase lag during cell division?

Accepted Answer

Aneuploidy — Anaphase lag (failure of pairing followed by random assortment) leads to aneuploidy.

Question 44

Why is monosomy involving an autosome incompatible with life?

Accepted Answer

Loss of essential genetic material — Autosomal monosomy is incompatible with life due to the loss of essential genetic material. ### SECTION G: STRUCTURAL CHROMOSOMAL ABNORMALITIES

Question 45

What type of chromosome rearrangement results in formation of one abnormally large chromosome and one extremely small one in Robertsonian translocation?

Accepted Answer

Transfer of segments between acrocentric chromosomes — Transfer of segments between acrocentric chromosomes leads to one large chromosome and one small one (usually lost).

Question 46

What happens to the isolated fragment lacking a centromere after deletion?

Accepted Answer

It almost never survives — Fragments lacking a centromere almost never survive during cell division.

Question 47

What type of structural abnormality is a ring chromosome considered to be?

Accepted Answer

Variant of deletion — A ring chromosome is a variant of a deletion where both ends of a chromosome are lost and the remaining ends fuse.

Complex Multigenic and Cytogenetic Disorders MCQs

Questions, Answers & Explanations