Genetics of Quantitative Traits

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Questions and Answers

What is currently the method of choice for delivering DNA into cells in gene therapy?

Adenoviruses (correct)

Particle bombardment

Electroporation

Direct injection

Which strategy helps to ensure that the correct cells are targeted in gene therapy?

Ex vivo gene therapy (correct)

Direct injection into blood

In vivo gene therapy

Electroporation

What effect can the immune response have on transgene expression in gene therapy?

Permanent expression of transgene

Reduction in transgene expression (correct)

No effect on transgene expression

Enhanced transgene expression

Which promoter type is utilized to restrict gene expression to specific tissues?

Tissue-specific promoters Signup and view all the answers

What potential outcome can result from exaggerated immune responses to gene therapy vectors?

Lethality of the gene therapy Signup and view all the answers

What is a common consequence of using adenoviruses in gene therapy trials?

Development of immunity against the adenovirus Signup and view all the answers

Which of the following challenges is associated with direct injection as a method of gene delivery?

Inefficiency that depends on the targeted tissue Signup and view all the answers

How can insulators be beneficial in gene therapy?

Mitigate inappropriate gene expression Signup and view all the answers

What was a significant risk associated with the transgene insertion during the gene therapy trial?

Disruption of a tumor-suppressor gene Signup and view all the answers

What complication did Jesse experience after participating in the gene therapy trial?

Massive immune reaction Signup and view all the answers

What was the cause of Leber congenital amaurosis (LCA)?

Mutations in a single gene important for vision Signup and view all the answers

What is the significance of the RPE65 gene in Leber congenital amaurosis?

Mutations in both copies are necessary for the disease. Signup and view all the answers

Which outcome did the gene therapy trial for SCID X-linked show for most of the boys involved?

Most boys developed a functional immune system Signup and view all the answers

What was a consequence of the transgene insertion into the LMO2 gene in the gene therapy trial?

Enhanced expression of the LMO2 protein Signup and view all the answers

What clinical manifestation is often associated with Leber congenital amaurosis?

Total blindness by age 30-40 Signup and view all the answers

Why might a previous infection sensitize the immune system to the adenovirus vector in gene therapy?

It causes an immune response that recognizes the vector as a threat. Signup and view all the answers

What are the primary components targeted by gene therapy in treating vision loss?

Retinal ganglion cells Signup and view all the answers

What is the main purpose of incorporating optogenetic components into retinal ganglion cells?

To enable the ganglion cells to respond to light Signup and view all the answers

Which innovative device processes visual information similar to the normal function of the retina?

Glasses with an onboard computer Signup and view all the answers

What is a significant limitation of gene therapy when photoreceptors are compromised?

The therapy may not provide a lasting solution Signup and view all the answers

What aspect of retinal prosthetics is currently developing in gene therapy?

Integrating viral delivery with optogenetic components Signup and view all the answers

What is the outcome of a maternal mutation in Drosophila?

The female will be sterile. Signup and view all the answers

Which type of cancer cell characteristic indicates a potential for immortality?

Uncontrolled growth. Signup and view all the answers

What is a unique feature of gap genes in Drosophila segmentation?

They affect the entire segment of the embryo. Signup and view all the answers

What effect does a mutation in proto-oncogenes have?

It can convert them to oncogenes. Signup and view all the answers

Which of the following best describes tumor suppressor genes?

They require two mutations for loss of normal function. Signup and view all the answers

What process is primarily responsible for the genomic instability seen in cancer cells?

Defects in gene repair mechanisms. Signup and view all the answers

In somatic gene therapy, what type of cells are targeted?

Somatic cells. Signup and view all the answers

What was the primary target for gene therapy in the first trial for SCID?

Adenosine deaminase (ADA) gene. Signup and view all the answers

Which evidence supports the multi-hit model of cancer?

Cancers are often found to be clonal descendants of one cell. Signup and view all the answers

What happens to the ADA substrate in T cells when there is a defect in the ADA gene?

It accumulates and becomes toxic. Signup and view all the answers

What distinguishes the gap genes from pair-rule genes in Drosophila?

Pair-rule genes create two segments at a time. Signup and view all the answers

Which gene is classified as a proto-oncogene?

RAS oncogene. Signup and view all the answers

What is the role of bicoid in Drosophila embryonic development?

Represses the expression of hunchback. Signup and view all the answers

What is a characteristic of a successful somatic gene therapy protocol for SCID?

Harvesting and reinfusing lymphocytes. Signup and view all the answers

What is the result of X inactivation in females, particularly concerning gene expression?

Some genes on the inactivated X chromosome may still be expressed. Signup and view all the answers

Which condition is characterized by having an extra chromosome 21?

Down syndrome Signup and view all the answers

In relation to genealogical studies, what does the term 'deletion loop' refer to?

A portion of a chromosome that is deleted and paired with its homologous chromosome. Signup and view all the answers

Which process is most likely to lead to phenotypic changes due to a gene imbalance?

Duplication Signup and view all the answers

What is a primary risk associated with chorionic villi sampling?

Higher rates of miscarriage due to procedural risks. Signup and view all the answers

In genetic terms, what does the concept of 'pseudodominance' imply?

An allele appears dominant when the corresponding recessive allele is deleted. Signup and view all the answers

What might happen during nonreciprocal translocations?

Genetic material is lost from one chromosome and added to another without exchange. Signup and view all the answers

Which of the following statements regarding inversions is true?

Inversions can prevent viable gamete production if they involve breakpoints within genes. Signup and view all the answers

What is a characteristic outcome of a Robertsonian translocation?

Loss of the shorter chromosome end. Signup and view all the answers

During which stage of prenatal development is amniocentesis generally performed?

Second trimester Signup and view all the answers

How does unequal crossing over contribute to genetic variation?

By causing variations in gene copy number. Signup and view all the answers

What is the potential effect of deletions on gene expression?

Haploinsufficiency due to gene imbalance. Signup and view all the answers

What is the role of a balancer chromosome in genetic studies involving Drosophila?

To prevent recombination and maintain the homozygous state. Signup and view all the answers

What does broad sense heritability (H2) indicate about phenotypic variation?

It measures the genetic variation in phenotype across the population. Signup and view all the answers

Which statement about narrow sense heritability (h2) is accurate?

High h2 indicates that offspring phenotypes can be predicted from parental phenotypes. Signup and view all the answers

What is the primary purpose of using quantitative trait loci (QTL) mapping?

To identify specific genes responsible for traits in individuals. Signup and view all the answers

How does a missense point mutation differ from a silent mutation?

It replaces one amino acid with another. Signup and view all the answers

What characteristic defines transposable elements in a genome?

They can move from one genomic location to another. Signup and view all the answers

What is the effect of dominance effects (Vd) on predictability in phenotypes?

They introduce variability that complicates predictions. Signup and view all the answers

In McClintock's experiment with corn, what role did the Ac element play?

It caused breakage of chromosome 9. Signup and view all the answers

Which classification of mutation replaces one base pair with another without altering the protein function?

Silent mutation. Signup and view all the answers

What does a LOD score of 3 or greater signify in genetic mapping?

Strong evidence of association between traits and genetic markers. Signup and view all the answers

How do induced mutations differ from spontaneous mutations?

Induced mutations are caused by external agents like chemicals or radiation. Signup and view all the answers

What type of mutation is characterized by a base pair change that results in a premature stop codon?

Nonsense mutation. Signup and view all the answers

What is the primary cause of frameshift mutations?

Insertion or deletion of base pairs causing a shift in the reading frame. Signup and view all the answers

Which mechanism is common to both retrotransposons and DNA transposons?

They are surrounded by repeat sequences that facilitate their movement. Signup and view all the answers

What does the C value paradox refer to in genetics?

Genome size does not correspond to the organism's phenotypic complexity. Signup and view all the answers

Study Notes

Additive

depends on the number of alleles present
phenotypic effect can be 0, 1, or 2
frequency is highest in the middle (bell curve)
additive inheritance: contributions of each locus add up without interaction
no dominance/epistasis

Genetic origins of a quantitative trait

Hypothesis 1: segregation of alleles at many loci; small, equal, and additive effects
Hypothesis 2: few genes; large additive effects
Polygenic: only genetics contribute to variation
Multifactorial: genetics and environmental factors influence variation

Environmental modifications

phenotype = genotype + environment
example: Siamese cat fur color (temperature affects enzyme function)
incomplete dominance: heterozygote phenotype is distinct from either homozygous

Quantitative Traits

genotype affects traits affected by multiple loci with additive effects
example: complementation, law of segregation, linkage
individual phenotypes are masked by environment; quantitative trait locus (QTL)
affected by environment

Lecture 13

how much of variation in phenotype is due to genetics vs environment?
P= G + E (phenotype)
Vp = Vg + Ve (variation)
Vg/Vp (heritability)
- how much phenotype variation is attributable to genetic variation
Broad Sense heritability (H²)= Vg/Vp
- H² =1 if all due to genotype
- H² =0 if all due to environment
H² is not predictive; tells why

Lecture 14

H² tells if phenotype is likely due to genotype in a specific family/population
H² does not predict progeny's phenotype based on parents'
Vp = Vg + Va + Vd + Vi
- Va - additive effects (predictive)
- Vd - dominance effects (not predictive)
- Vi - epistatic effects (not predictive)
narrow-sense heritability (h²) = Va / Vp
- h²=1 if all due to additive effects
- h²=0 if nothing due to additive effects
h² tells if phenotype of individual is predictable based on family
h² does not tell if genes/alleles affect other families

Lecture 15

More inbreeding = less heterozygosity
candidate genes in QTL are identified by fine-mapping
recombinant chromosomes (NILs) fine-map QTL to single gene
expression of the candidate gene examined using PCR
protein sequence analyzed for function

Mutations

Mutations affecting phenotype are rare
forward mutation (WT to mutant allele)
reverse mutation (mutant to WT)
classifications:
- base substitution
- transition
- transversion
- deletion
- insertion
- indels
- inversion
- reciprocal translocation

Lecture 16

Point mutations (silent, missense)
Ratio of synonymous/non-synonymous mutations measures selection strength (some mutations are favored over others in evolution)
nonsense mutations: stop codon replacement
frameshift mutations: insert/delete base pairs changing reading frame
intragenic suppressor mutations
Mutations outside the coding sequence (splice donor/acceptor site mutations)
large mRNA/RNA results in slower northern/western blots
loss of function alleles - typically recessive (null or hypomorphic)
gain of function mutations (hypermorphic or neomorphic)

Lecture 17

Chromosomal packaging: nucleosomes
Heterochromatin: tightly packed
Chromatin remodelling: altering chromatin structure
X chromosome inactivation: one X chromosome inactivated in females, hereditary
Euploidy, polyploidy, aneuploidy (chromosome number variations)
Nondisjunction: errors in chromosome segregation in meiosis/mitosis
Monosomy, trisomy, nullisomy, tetrasomy
Pathogenesis: development of unfertilized egg into embryo (without fert.); usually lethal

Lecture 18

Polyploidy: additional sets of chromosomes (autopolyploids: same species; allopolyploids: different species)
Tetraploid meiosis (new ratio 1:4:1)
Meiotic nondisjunction: both sets of a chromosome go into one cell
Monosomy, trisomy, nullisomy, tetrasomy, etc. genetic disorders
Prenatal testing: screening (not diagnostic) in first trimester; diagnostic tests (chorionic villi sampling, amniocentesis)
Fetal testing; look for abnormal karyotypes; screening of biochemical/molecular disorders
Polytene chromosomes: model structure allowing visualization of banding patterns
Deletions: x-rays, intragenic (small), multigenic (many), haploinsufficiency
Deletion loop
Pseudodominance

Lecture 19

Differences in phenotypes due to epigenetics
Epigenetics: heritable modifications in gene function (not due to base sequence changes)
Molecular mechanisms:
1. DNA methylation (CpG islands = gene repression)

Lecture 20

Gene therapy: correcting diseased phenotype by introducing/correcting genes in body cells
somatic gene therapy: does not change germline (sperm/egg cells)
Proto-oncogenes and tumor suppressor genes - gain/loss of function mutations
Oncogenes: promote cell growth (dominant); TS genes: inhibit growth (recessive)
Examples of mutations: mutating receptor kinases in oncogenes, RB (tumor suppressor)

Lecture 21

Gene therapy protocol, effects of ADA deficiency (severe combined immunodeficiency, SCID)
vectors
- adeno-associated virus
- adenovirus
- herpes
- retrovirus
challenges of gene therapy: correct cells targeted, appropriate expression levels for time, consequences of immune responses to vector/transgene products

Lecture 22

Somatic gene therapy

Lecture 23

Risks of gene therapy: transgene integration into functional genes, consequences
Gene therapy trial (France): SCID X-linked

Lecture 24

Abnormal eye disorders
RPE65 mutations
Animal model of LCA
Human clinical trials; RPE65 gene therapy

Lecture 25

future of gene therapy: prosthetics & optogenetics
developing gene therapy targeting retinal ganglion cells
mimicking retina's normal visual processing

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Description

This quiz explores the principles of additive inheritance and the genetic origins of quantitative traits. It examines how multiple alleles contribute to phenotypic variation, as well as the impact of environmental factors on genotype expression. Test your understanding of concepts like polygenic traits and incomplete dominance.