Q: Which equation best represents the additive effect of multiple genes on a quantitative trait, such as height?

$$\text{Phenotype} = G_1$ + G_2$ + G_3$ + \ldots + G_n + E$$

Question 1

Which of the following best describes polygenic inheritance, as illustrated by the distribution of human skin color in the population?

Accepted Answer

Multiple genes contribute additively to a phenotype, resulting in a continuous variation.

Question 2

Genome-wide association studies (GWAS) rely on which principle to identify genes associated with human traits?

Accepted Answer

Closely linked polymorphisms are inherited together because of limited recombination.

Question 3

A Manhattan plot from a GWAS shows several 'skyscrapers' of significant SNP associations across chromosomes. What does a high point on the y-axis represent?

Accepted Answer

A SNP with a strong statistical association to the phenotype or disease.

Question 4

Which equation best represents the additive effect of multiple genes on a quantitative trait, such as height?

Accepted Answer

$$	ext{Phenotype} = G_1$ + G_2$ + G_3$ + \ldots + G_n + E$$

Question 5

In the context of hemoglobin gene families, which statement is correct regarding their expression during human development?

Accepted Answer

Embryonic hemoglobin (HbE) is expressed during the first 3 months of pregnancy, followed by fetal hemoglobin (HbF) until about 6 months after birth.

Question 6

A missense mutation in the $$\beta-$$globin gene causes sickle-cell disease. Which amino acid change is responsible?

Accepted Answer

Glutamate to Valine

Question 7

Which therapeutic approach has shown promise in curing sickle-cell disease and $$\beta-$$thalassemia by increasing fetal hemoglobin (HbF) levels?

Accepted Answer

Induction of HbF expression by disrupting BCL11A enhancer using CRISPR

Question 8

What is the function of BCL11A in the regulation of the $$\gamma-$$globin gene?

Accepted Answer

BCL11A acts as a repressor of $$\gamma-$$globin gene transcription.

Question 9

A CRISPR-Cas9 strategy targets the enhancer in intron 2 of the BCL11A gene. What is the expected outcome for hemoglobin expression?

Accepted Answer

Decreased expression of BCL11A and increased HbF levels.

Question 10

Which of the following best explains why sickle-cell disease persists at high frequency in certain populations?

Accepted Answer

Heterozygotes have a selective advantage against malaria.

Question 11

In a GWAS for Crohn’s disease, several loci are identified. What does this suggest about the genetic architecture of Crohn’s disease?

Accepted Answer

Crohn’s disease is polygenic, with multiple loci contributing to susceptibility.

Question 12

Which equation represents the probability of association in a GWAS Manhattan plot?

Accepted Answer

$$-\log_{10}(p)$$

Question 13

A patient with hereditary persistence of fetal hemoglobin (HPFH) has elevated HbF levels as an adult. Which genetic change is most likely responsible?

Accepted Answer

A deletion or SNP in the $$\gamma-$$globin gene promoter.

Question 14

Which of the following is a real-world application of CRISPR-Cas9 in treating genetic disorders?

Accepted Answer

Editing the enhancer in BCL11A to increase HbF and cure sickle-cell disease.

Question 15

Which process is most likely to occur after CRISPR-Cas9 creates a double-strand break in DNA without a repair template?

Accepted Answer

Non-homologous end joining (NHEJ)

Question 16

In the context of GWAS, why are large sample sizes important?

Accepted Answer

To increase statistical power and detect small effect sizes.

Question 17

Which of the following best describes the relationship between SNPs identified in GWAS and causative mutations?

Accepted Answer

SNPs identified in GWAS are often linked to causative mutations but may not be causative themselves.

Question 18

Which transcription factor binds to the TGACCA motif in the $$\gamma-$$globin gene promoter and represses its expression?

Accepted Answer

BCL11A

Question 19

A patient receives CRISPR-edited stem cells targeting the BCL11A enhancer. What is the expected clinical outcome?

Accepted Answer

Increased fetal hemoglobin (HbF) and relief of symptoms from sickle-cell disease or $$\beta-$$thalassemia.

Polygenic Inheritance, GWAS, and CRISPR Applications in Human Genetics

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