Molecular Polymorphism: GNSA 510 Part 1

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is a characteristic of copy number variations (CNVs)?

They are always balanced translocations.

They have no impact on gene function.

They always consist of inversions.

They can lead to disease via dosage sensitivity. (correct)

Which genetic mechanism is associated with CNVs?

Unequal crossing over. (correct)

Chromosomal breaks and rejoining.

Balanced translocations.

Gene regulation changes.

What condition is caused by a trinucleotide CAG repeat in the FMR-1 gene?

Hemophilia A.

Prader-Willi syndrome.

Cri-du-chat syndrome.

Fragile X Syndrome. (correct)

Which of the following is true regarding non-CNVs such as inversions and balanced translocations?

They can affect gene function without causing dosage effects. Signup and view all the answers

What is a common cause of autism according to the genetic studies mentioned?

Single gene Mendelian inheritance. Signup and view all the answers

What are insertions and deletions (INDELS) also known as?

Deletion and insertion polymorphisms Signup and view all the answers

Why is Sanger Sequencing considered the gold standard for genome sequencing projects?

It has proven accuracy and reliability in large resequencing projects. Signup and view all the answers

What capability does Mutation Surveyor provide in the detection of INDELS?

It automates calls of heterozygous and homozygous INDELS. Signup and view all the answers

What conditions can be caused by indels?

Tay-Sachs disease and various forms of cancer Signup and view all the answers

What accuracy does Mutation Surveyor achieve in detecting INDELS with specific sequencing conditions?

Greater than 99% accuracy when using bi-directional sequences of greater than Plured 20 Signup and view all the answers

What describes a de novo deletion?

A deletion that occurs spontaneously Signup and view all the answers

Which CNV type leads to an increase in gene expression?

Duplication Signup and view all the answers

What can result from a genomic imbalance due to CNVs?

Congenital anomalies Signup and view all the answers

Which of the following gene types are enriched in copy number variations?

Brain development and immune system genes Signup and view all the answers

Which CNV type involves the exchange of segments between two different chromosomes?

Translocation Signup and view all the answers

What is a likely consequence of an insertion in the genome?

Altered gene expression Signup and view all the answers

What can an inversion in DNA lead to?

Novel gene fusion Signup and view all the answers

Which statement about inherited duplications is correct?

They are inherited from a parent. Signup and view all the answers

Which of the following methods is not used to identify indels?

Polymerase Chain Reaction Signup and view all the answers

What are the two possible origins of copy number variations (CNVs)?

Inherited and De novo Signup and view all the answers

Which type of CNV involves a segment of DNA being flipped within the genome?

Inversion Signup and view all the answers

What describes the outcome of a deletion CNV?

Complete gene loss Signup and view all the answers

Which of the following CNV types can potentially result in the production of novel fusion genes?

Translocation Signup and view all the answers

What is a common source of CNVs during the production of germ cells?

Non-allelic Homologous Recombination Signup and view all the answers

What does a duplication event in DNA typically lead to?

Increased gene dosage leading to phenotypic changes Signup and view all the answers

Which of the following characteristics can a CNV NOT exhibit?

Exclusively affecting non-coding regions Signup and view all the answers

What is the primary effect of INDELs that are not a multiple of 3 in coding regions?

They can lead to frameshift mutations. Signup and view all the answers

Which INDEL class involves inserting random DNA sequences?

INDELs containing random DNA sequences Signup and view all the answers

Which type of polymorphism originates from a single mutation effect?

INDELs Signup and view all the answers

How can INDELs be utilized in forensic analysis?

As genetic markers in studies of phylogenetic relationships Signup and view all the answers

What percentage of the variants on human chromosome 22 were identified as INDEL polymorphisms?

13% Signup and view all the answers

For which regions can INDELs that are multiples of 3 altering transcriptional activity occur?

Promoter regions Signup and view all the answers

What role do comprehensive variation maps serve compared to SNP maps alone?

They enhance the identification of variants by integrating SNPs and INDELs. Signup and view all the answers

Which of the following statements regarding INDELs is incorrect?

They have high mutation rates compared to SNPs. Signup and view all the answers

What is the primary hypothesis tested in relation to CNVs in autism spectrum disorder families?

Identifying CNVs related to distant relatives could uncover novel ASD susceptibility genes. Signup and view all the answers

Which of the following best describes the significance of CNVs in genetic studies?

They contribute to phenotypic heterogeneity and understanding genetic conditions. Signup and view all the answers

What is one of the key uses of mapping and identifying CNVs?

To target chromosomal rearrangements causing developmental defects. Signup and view all the answers

Which technology is NOT mentioned as a method for identifying CNVs?

SNP genotyping Signup and view all the answers

How does the size of CNVs compare to SNPs?

CNVs are generally much larger, spanning from 100 bp to 3 Mb. Signup and view all the answers

What percentage of the reference genome is covered by CNVs compared to SNPs?

CNVs cover 29.74% and SNPs cover less than 1%. Signup and view all the answers

Which of the following is NOT a type of CNV mentioned?

Insertion Signup and view all the answers

What role do SNPs play in linkage disequilibrium?

They help identify demographic events and candidate genes. Signup and view all the answers

Study Notes

Molecular Polymorphism: Pharmaco-Toxicogenomic GNSA 510 (Part 1)

SNPs are variations in DNA sequences
SNPs display abundance, classification (SNP type, alleles, CNVs/Indels), distributions (genomic position, intra/inter-population)
LD (linkage disequilibrium) and haplotypes are relevant concepts
Paper analysis of SNPs involves application technology, detection techniques (genotyping), and inherited disease implications

INDELS

INDELs (insertions or deletions) can change the nucleotide sequence count
Coding regions with INDELs can affect the length of an INDEL, potentially causing frameshift mutations or premature termination codons
Non-coding regions with INDELs can affect transcriptional activity
The length of an INDEL is often a multiple of 3 in non-coding regions

Chromosome 22 and INDEL Polymorphisms

Early studies focused on variations on chromosome 22
13% of variants on chromosome 22 were INDEL polymorphisms

Five Major INDEL Classes

Insertions or deletions of simple base pairs
Monomeric base pair expansions
Multi-base pair expansions (e.g., 2-15 bp repeat units)
Transposon insertions
INDELs with random DNA sequences (ranging from 2 to 9,989 bp)

Importance of INDELS

Alter human phenotypes and cause diseases
Used in forensic analysis
Used as genetic markers in natural populations (especially in phylogenetic studies)
These polymorphisms originate from single mutations and have low mutation rate advantages over STRs

Mapping INDELS

Useful to integrate human INDEL variation maps into HapMap
A complete description of variation in haplotype blocks would help identify specific variations
Comprehensive maps (including both SNPs and INDELs) are more effective than SNP maps for identifying variants

Identification of INDELS

Identification uses short or long reading sequencing, aCGH/exome sequencing, and GWAS

Detection of Insertions and Deletions (INDELS)

INDELS can lead to significant genetic diseases (e.g., Tay-Sachs disease, Alzheimer's, other cancer forms)
Mutation Surveyor software is used to detect both homo/heterozygous INDELS
This software compares sample mobility to a reference trace and realigns sequences for better accuracy (greater than 99% accuracy for sequences of 20+ bp)

Definition of CNVs

CNVs (copy number variations) are changes in the number of copies of a DNA segment
CNVs have diverse origins (inherited or de novo)
CNVs show quantitative variation and can be located in target regions (e.g., single genes, dozens of genes, or no genes)

CNV Types

Duplication
Deletion
Translocation
Insertion
Inversion

Sources of CNVs

Non-allelic homologous recombination (NAHR) is a primary source
NAHR during meiosis leads to deletions or duplications in germ cells
The presence of segmental duplications supports the NAHR theory

Deletion and Duplication

De novo deletion vs. inherited duplication
CNVs shown in family diagrams

Clinical Impact of CNVs

Gene dosage-sensitive genes
Genomic imbalance-related congenital anomalies

Genes Involved in Copy Number Variation

Genes involved in brain development and activity, immune system functions, and cell division are often spared, suggesting that other functions that have evolved rapidly in humans tend to be enriched in CNVs

Mapping and Identifying CNVs

Used for identifying genes that cause common diseases/deficiencies
Contribute to more accurate and complete human genome references
Exclude variations in unaffected individuals to target chromosomal rearrangements

CNV vs. SNP

CNVs are larger changes in DNA segments than SNPs (single nucleotide polymorphisms)
CNVs affect a larger portion of the genome than SNPs
CNV numbers total 38,406 in a given database (for comparison, SNPs total 14,708,752)

SNP Distribution

SNPs are useful to examine linkage disequilibrium, recombination rates, and association with complex traits
SNPs can help map complex traits, aid in fine mapping, and highlight demographic events that shaped population variation
SNPs can identify candidate genes and inform study selection

CNVs that Cause Disease

Fragile X Syndrome's trinucleotide repeat causes a decreased quantity of fragile X protein (FRP) causing the syndrome.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Explore the world of molecular polymorphism in this quiz based on GNSA 510. Learn about SNPs, INDELs, and their implications in pharmacogenomics and toxicogenomics. Delve into crucial concepts like linkage disequilibrium, haplotypes, and chromosome 22 variations.