variation

Question 1

What are Single-Nucleotide Polymorphisms (SNPs)?

Answer 1

SNPs are the most common type of genetic variation, involving a change in a single nucleotide base (A, T, C, or G). They occur approximately once every 300 bases in the human genome and can influence various traits.

Question 2

What are Insertion and Deletion Variations (Indels)?

Answer 2

Indels refer to the addition or loss of one or more nucleotide bases in a DNA sequence. They can range from a few base pairs to thousands of base pairs and can lead to frameshift mutations.

Question 3

What are Copy Number Variations (CNVs)?

Answer 3

CNVs involve variations in the number of copies of specific genes or genomic regions. These variations can affect gene dosage and contribute to phenotypic diversity and disease susceptibility.

Question 4

What are Structural Variations?

Answer 4

Structural variations encompass larger genomic alterations, including translocations, inversions, and duplications. They can disrupt gene function and are often implicated in cancer and other genetic disorders.

Question 5

What are Chromosomal Abnormalities?

Answer 5

Chromosomal abnormalities include changes in chromosome number (e.g., aneuploidy) or structure that can lead to serious developmental issues or diseases, such as Down syndrome caused by trisomy of chromosome 21.

Question 6

What is Polyploidy?

Answer 6

Polyploidy is a condition where an organism has more than two complete sets of chromosomes (e.g., triploid or tetraploid). It is common in plants and some animal species and can lead to increased size and vigor.

Question 7

What are Transposable Elements?

Answer 7

Transposable elements, also known as ‘jumping genes,’ are sequences that can change their position within the genome. They can create mutations and contribute to genetic diversity.

Question 8

Aspect

Answer 8

SNP

Question 9

Definition

Answer 9

A variation at a single nucleotide position occurring in at least 1% of the population.

Question 10

Frequency

Answer 10

Occurs at least 1% in the population; considered common.

Question 11

Population vs. Individual Level

Answer 11

Considered in the context of populations; represents stable variations.

Question 12

Types of Changes

Answer 12

Specifically involves changes in a single nucleotide.

Question 13

Impact on Function

Answer 13

Generally minimal impact but can influence traits and disease susceptibility.

Question 14

Example

Answer 14

Change from adenine (A) to cytosine (C) found significantly in the population.

Question 15

What are synonymous mutations?

Answer 15

Synonymous mutations are point mutations that do not change the amino acid sequence of the resulting protein due to the redundancy of the genetic code.

Question 16

What is the impact of synonymous mutations?

Answer 16

They can affect translational efficiency, mRNA stability, and splicing, influencing gene expression levels.

Question 17

Can synonymous mutations be silent?

Answer 17

Yes, they are often viewed as silent but can still have significant effects on protein synthesis and function.

Question 18

Give an example of a synonymous mutation.

Answer 18

A synonymous mutation in the MDR1 gene introduces a rare codon that slows down translation, allowing for proper cotranslational folding.

Question 19

What are nonsynonymous mutations?

Answer 19

Nonsynonymous mutations are point mutations that result in a change in the amino acid sequence of a protein.

Question 20

What is the impact of nonsynonymous mutations?

Answer 20

They can lead to loss of function or gain of function in proteins, significantly affecting their activity.

Question 21

Give an example of a nonsynonymous mutation.

Answer 21

A missense mutation in the TP53 gene may alter its ability to regulate cell cycle and apoptosis, contributing to cancer development.

Question 22

Missense mutation

Answer 22

Missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid

Question 23

Nonsense mutation.

Answer 23

Nonsense mutations are mutations that change an amino acid to a stop codon.

Question 24

What is an indel?

Answer 24

An indel is a mutation that involves the insertion or deletion of one or more nucleotides in a genomic sequence.

Question 25

What are single nucleotide indels?

Answer 25

Single nucleotide indels refer to the insertion or deletion of a single nucleotide in a DNA sequence.

Question 26

What is a frameshift mutation?

Answer 26

A frameshift mutation occurs when an indel’s length is not a multiple of three, altering the reading frame and potentially resulting in different protein products.

Question 27

How common are indels in human genomes?

Answer 27

Indels are common, with estimates suggesting several million indels present in human genomes.

Question 28

What types of changes do indels encompass?

Answer 28

Indels encompass insertions (adding nucleotides) and deletions (removing nucleotides) from the DNA sequence.

Question 29

What are microindels?

Answer 29

Microindels are small insertions or deletions that often involve just a few base pairs and can lead to frameshift mutations if they occur within coding regions.

Question 30

What is the significance of indels as genetic markers?

Answer 30

Indels serve as important genetic markers in population genetics and phylogenetic studies, helping identify species and understand evolutionary relationships.

Question 31

What clinical relevance do indels have?

Answer 31

In clinical genomics, indels are associated with various diseases and conditions and may influence responses to targeted therapies.

Question 32

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Answer 32

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Question 33

What is genetic variation?

Answer 33

Genetic variation is defined as a permanent change in the DNA sequence that makes up a gene.

Question 34

What are the types of genetic variation?

Answer 34

Types include polymorphisms (e.g., SNPs), small insertions/deletions (Indels), copy number variations (CNVs), and complex genetic variations (e.g., translocations, inversions).

Question 35

What is a VCF file format?

Answer 35

VCF (Variant Call Format) is used to record information about genetic variants in genomes, such as SNPs, Indels, and CNVs, suitable for mutation screening.

Question 36

What is the counting SNPs method?

Answer 36

The counting method involves counting alleles at each site for individuals separately and using cut-off rules to call a SNP or genotype.

Question 37

What is the common cutoff used in SNP calling?

Answer 37

The most common cutoff is a Phred-type quality score of Q30, which corresponds to a 0.1% error rate in base calling.

Question 38

What is the variant calling workflow?

Answer 38

The workflow includes raw sequencing, quality control, alignment to the genome, post-alignment cleanup, variant calling, annotation, visualization (IGV), and prioritization/filtering.

Question 39

What are the steps for prioritizing functional mutations?

Answer 39

1. Use a Q30 filter to obtain high-confidence bases. 2. Count alleles at each site. 3. Call heterozygous genotype if the non-reference allele proportion is between 20% and 80%; otherwise call homozygous.

Question 40

What is a limitation of the counting method?

Answer 40

The sequence depth needs to be higher than 20x; thus, the probability of a heterozygous individual falling outside the 20-80% range is small.

Question 41

What are probabilistic methods in variant calling?

Answer 41

Probabilistic methods involve analyzing the biological significance and disease relevance of variants through models predicting their effects on protein structure and function.

Question 42

What does genetic variation identification involve?

Answer 42

Genetic variation identification involves detecting mutation types within the genome.

Question 43

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Answer 43

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Question 44

What is variant annotation?

Answer 44

Variant annotation involves analyzing the biological significance and disease correlation of genetic variants.

Question 45

What are the key aspects of variant annotation?

Answer 45

Key aspects include predicting the biological function of a variant, determining if it alters protein structure or amino acids, identifying if it is synonymous or nonsynonymous, assessing its impact on stop or start codons, and checking if it is located in regulatory regions.

Question 46

What is the purpose of filtering variants?

Answer 46

Variants are filtered to classify and rank them based on biological significance and disease relevance.

Question 47

What types of genetic variations are analyzed during variant annotation?

Answer 47

Types include single nucleotide polymorphisms (SNPs), small insertions/deletions (Indels), and copy number variations (CNVs).

Question 48

What does the genetic variation identification process involve?

Answer 48

It involves detecting mutation types within the genome using various methods and tools.

Question 49

What is the role of computational models in variant annotation?

Answer 49

Computational models help predict the biological function of variants, including their effects on protein structure and function.

Question 50

How does one determine if a mutation is synonymous or nonsynonymous?

Answer 50

By analyzing whether the mutation changes the amino acid sequence of the resulting protein.

Question 51

What regulatory regions are considered during variant annotation?

Answer 51

Regulatory regions include promoters and transcription factor binding sites that may influence gene expression.

Question 52

What is the significance of identifying variants in regulatory regions?

Answer 52

Variants in regulatory regions can affect gene expression levels and contribute to phenotypic variation or disease susceptibility.

Question 53

What is four-layer filtering in variant screening?

Answer 53

Four-layer filtering categorizes and prioritizes variants based on their biological significance and relevance to diseases.

Question 54

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Answer 54

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Question 55

What is four-layer filtering in variant screening?

Answer 55

Four-layer filtering is a systematic approach used to prioritize and classify genetic variants based on their biological significance and relevance to diseases.

Question 56

What is the purpose of four-layer filtering?

Answer 56

The primary goal is to refine the list of genetic variants to those most likely to be clinically relevant or biologically significant.

Question 57

What are the key steps in four-layer filtering?

Answer 57

1. Quality Control 2. Functional Annotation 3. Clinical Relevance 4. Prioritization and Ranking.

Question 58

What does Layer 1 involve in four-layer filtering?

Answer 58

Layer 1 involves applying quality control measures to ensure only high-confidence variants are considered.

Question 59

What happens in Layer 2 of four-layer filtering?

Answer 59

Variants are annotated for their potential impact on protein function, including determining if they are synonymous or nonsynonymous.

Question 60

How does Layer 3 assess clinical relevance?

Answer 60

Variants are evaluated for their association with known diseases or phenotypes using databases of clinically relevant mutations.

Question 61

What is done in Layer 4 of four-layer filtering?

Answer 61

Variants are prioritized based on combined scores from previous layers to focus on promising candidates.

Question 62

What are the benefits of four-layer filtering?

Answer 62

Enhanced accuracy, streamlined analysis, and improved clinical application by identifying actionable variants.