COMPLEX MULTIGENIC AND CYTOGENETIC DISORDERS - 50 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, demonstrating that different polymorphisms vary significantly in their contribution. ---

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 diabetic 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

A chromosome number of 3n is classified as

Accepted Answer

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

Question 7

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 8

What is the chromosome count in a trisomic zygote?

Accepted Answer

Mostly unchanged in early disease — When a gamete with an extra chromosome (n + 1) is fertilized by a normal gamete (n), the resulting zygote is trisomic with chromosome count of 2n + 1. ---

Question 9

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

Accepted Answer

Sex chromosome imbalances — Imbalances of sex chromosomes (excess or loss) are tolerated much better than similar imbalances of autosomes, often producing subtle abnormalities. --- ## SECTION B: CHROMOSOMAL TERMINOLOGY & NOTATION (Questions 11-16) ---

Question 10

What does mosaicism refer to in cytogenetics?

Accepted Answer

Mosaicism — Mosaicism is the presence of two or more populations of cells with different complements of chromosomes in the same individual, commonly affecting sex chromosomes. ---

Question 11

In cytogenetic notation, what does "p" represent?

Accepted Answer

Short arm (petit) — In cytogenetic shorthand, "p" (French, petit) denotes the short arm of a chromosome, while "q" denotes the long arm. ---

Question 12

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 at region 3, band 1, and the short arm of chromosome 5, region 1, band 4. ---

Question 13

What is a Robertsonian translocation?

Accepted Answer

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

Question 14

What is the most common isochromosome found in live births?

Accepted Answer

i(Xq) — The most common isochromosome present in live births involves the long arm of the X chromosome and is designated i(Xq), resulting in monosomy for Xp genes and trisomy for Xq genes. ---

Question 15

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 remaining arm. --- ## SECTION C: DOWN SYNDROME (TRISOMY 21) (Questions 17-27) ---

Question 16

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, with a chromosome count of 47, most commonly caused by meiotic nondisjunction. ---

Question 17

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

Accepted Answer

1 in 25 — Down syndrome occurs in 1 in 1550 live births in women younger than 20 years but increases dramatically to 1 in 25 live births in women older than 45 years. ---

Question 18

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

Accepted Answer

95% — In 95% of Down syndrome cases, the extra chromosome is of maternal origin, supporting that meiotic nondisjunction occurs primarily in the ovum. ---

Question 19

What percentage of Down syndrome cases result from translocation?

Accepted Answer

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

Question 20

What percentage of Down syndrome patients are mosaics?

Accepted Answer

10% — Approximately 1% of patients with trisomy 21 are mosaics, usually having a mixture of 46- and 47-chromosome cells resulting from mitotic nondisjunction during embryogenesis. ---

Question 21

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 including atrial septal defects and ventricular septal defects. ---

Question 22

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, including both acute lymphoblastic leukemias and acute myeloid leukemias. ---

Question 23

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

Accepted Answer

25 years — Improved medical care has increased the longevity of persons with trisomy 21, with the current median age at death being 47 years, up from 25 years in 1983. ---

Question 24

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

Accepted Answer

T cell functions — Patients with Down syndrome demonstrate abnormal immune responses affecting mainly T cell functions, predisposing them to serious infections and thyroid autoimmunity. ---

Question 25

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

Accepted Answer

25 to 50 — Down syndrome is a leading cause of severe mental retardation, with approximately 80% of those afflicted having an IQ of 25 to 50. --- ## SECTION D: OTHER AUTOSOMAL DISORDERS (Questions 28-30) ---

Question 26

What is the chromosomal abnormality in Patau syndrome?

Accepted Answer

Trisomy 13 — Patau syndrome is caused by trisomy 13, occurs less commonly than trisomy 21, and is associated with increased maternal age and severe malformations. ---

Question 27

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

Accepted Answer

Chromosome 22 — The 22q11.2 deletion syndrome results from a small interstitial deletion of band 11 on the long arm of chromosome 22. ---

Question 28

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 were previously believed to be different disorders but are now known to both be caused by 22q11.2 deletion. ---

Question 29

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 22q11.2 deletion syndrome, as its loss seems to correlate with the occurrence of DiGeorge syndrome. ---

Question 30

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

Accepted Answer

Fluorescence in situ hybridization (FISH) — The diagnosis of 22q11.2 deletion syndrome can be established only by detection of the deletion using fluorescence in situ hybridization (FISH). ---

Question 31

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

Accepted Answer

Hypocalcemia — Parathyroid hypoplasia in DiGeorge syndrome results in hypocalcemia, which is one of the characteristic features of the condition. --- ## SECTION F: COMPLEX INHERITANCE & GENETIC CONCEPTS (Questions 37-44) ---

Question 32

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

Accepted Answer

Many polymorphisms with modest effects are co-inherited — Complex multigenic disorders occur when many polymorphisms, each with a modest effect and low penetrance, are co-inherited according to this hypothesis. ---

Question 33

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 in type 1 diabetes, 6 or 7 are considered most important, demonstrating that polymorphisms vary in significance. ---

Question 34

In general, which produces more severe defects?

Accepted Answer

Loss of chromosomal material — In general, loss of chromosomal material (deletion, monosomy) produces more severe defects than does gain of chromosomal material (trisomy). ---

Question 35

What is the outcome of polyploidy in most cases?

Accepted Answer

Spontaneous abortion — Polyploidy, which refers to exact multiples of the haploid number such as 3n and 4n, generally results in spontaneous abortion. ---

Question 36

What is the result of anaphase lag during cell division?

Accepted Answer

Aneuploidy — Failure of pairing of homologous chromosomes followed by random assortment (anaphase lag) can lead to aneuploidy. ---

Question 37

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 — In Robertsonian translocation, the transfer of segments between acrocentric chromosomes leads to formation of one abnormally large chromosome and one extremely small one that is usually lost. ---

Question 38

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

Accepted Answer

It almost never survives — After deletion with two interstitial breaks, the isolated fragment which lacks a centromere almost never survives, and thus many genes are lost. ---

Question 39

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

Accepted Answer

Variant of deletion — A ring chromosome is considered a variant of deletion where, after loss of segments from each end of the chromosome, the arms unite to form a ring. ---

Question 40

In most chromosomal disorders, what is the typical pattern of inheritance?

Accepted Answer

De novo changes — In most cases, chromosomal disorders result from de novo changes (parents are normal, and risk of recurrence in siblings is low). ---

Question 41

Which form of Down syndrome is an important exception to the low recurrence risk principle?

Accepted Answer

Translocation form of Down syndrome — An uncommon but important exception to the low recurrence risk is exhibited by the translocation form of Down syndrome, which can be inherited from a parent who is a carrier. ---

Question 42

What psychiatric conditions are patients with 22q11.2 deletion at particularly high risk for?

Accepted Answer

Schizophrenia and bipolar disorder — In addition to malformations, patients with 22q11.2 deletion are at particularly high risk for psychoses such as schizophrenia and bipolar disorder. --- ## ANSWER KEY Section A (1-10): B, C, B, C, C, B, B, C, C, C Section B (11-16): B, C, B, B, B, B Section C (17-27): C, C, D, B, A, C, C, B, C, B, B Section D (28-30): B, A, B Section E (31-36): C, B, B, C, B, C Section F (37-44): B, B, B, A, C, B, B, B Section G (45-50): C, C, B, D, C, B --- ## SCORING GUIDE - 45-50 correct: Excellent - Well prepared for exam - 40-44 correct: Very Good - Minor review needed - 35-39 correct: Good - Review weak areas - 30-34 correct: Fair - Significant review n

COMPLEX MULTIGENIC AND CYTOGENETIC DISORDERS - 50 MCQs

Questions, Answers & Explanations