Genetic Mutations and Their Effects
43 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Missense mutations cause no change in the sequence of the encoded protein.

False (B)

Nonsense mutations occur when a nucleotide substitution converts an amino acid codon into a stop codon.

True (A)

Silent mutations always lead to a change in the encoded protein.

False (B)

Dynamic mutations involve expansions of repeat sequences within the DNA.

<p>True (A)</p> Signup and view all the answers

Deletions and insertions of a small number of bases account for 50% of disease-causing mutations.

<p>False (B)</p> Signup and view all the answers

Long-range regulatory mutations are common in human genetic disease.

<p>False (B)</p> Signup and view all the answers

RNA processing mutations can destroy consensus splice sites.

<p>True (A)</p> Signup and view all the answers

Nucleotide substitutions are the most prevalent type of mutation, accounting for 60% of all disease-causing mutations.

<p>True (A)</p> Signup and view all the answers

Hotspots of mutation are locations in the genome where mutations occur more frequently than expected.

<p>True (A)</p> Signup and view all the answers

There are only two types of mutations, which are base pair substitutions and deletions.

<p>False (B)</p> Signup and view all the answers

Nonhomologous end-joining repair involves a precise matching of the broken ends of DNA before they are joined.

<p>False (B)</p> Signup and view all the answers

The overall mutation rate due to replication errors in the human genome is approximately 10 mutations per cell division.

<p>False (B)</p> Signup and view all the answers

Nucleotide substitutions can occur due to spontaneous chemical processes and may not always be accurately repaired.

<p>True (A)</p> Signup and view all the answers

Transitions involve changes from purine to purine or pyrimidine to pyrimidine.

<p>False (B)</p> Signup and view all the answers

Transversions are more prevalent than transitions in the human genome as a result of random nucleotide substitutions.

<p>False (B)</p> Signup and view all the answers

Methylation of cytosine residues in the human genome is responsible for generating the majority of mutations.

<p>True (A)</p> Signup and view all the answers

Hotspots of mutation in the human genome do not show significant preference for specific types of nucleotide substitutions.

<p>False (B)</p> Signup and view all the answers

The estimated average rate of new mutations in human genomes is about 1.2 × 10−8 mutations per base pair per generation.

<p>True (A)</p> Signup and view all the answers

More than 30% of single nucleotide substitutions arise from spontaneous deamination.

<p>True (A)</p> Signup and view all the answers

DNA repair mechanisms are highly efficient in correcting nucleotide changes resulting from DNA damage.

<p>False (B)</p> Signup and view all the answers

Mutation rates can vary from gene to gene and from individual to individual.

<p>True (A)</p> Signup and view all the answers

C>T transitions are equally common as G>A transitions among single base pair substitutions.

<p>False (B)</p> Signup and view all the answers

The CG doublet is not considered a hotspot for mutations in the human genome.

<p>False (B)</p> Signup and view all the answers

Frameshift mutations can occur only when a deletion of three nucleotides takes place.

<p>False (B)</p> Signup and view all the answers

Capping, polyadenylation, and splicing are essential modifications needed during the conversion of RNA transcripts to mature mRNAs.

<p>True (A)</p> Signup and view all the answers

The 5' donor and 3' acceptor sites are critical for the proper splicing of introns from unprocessed RNA.

<p>True (A)</p> Signup and view all the answers

Insertions and deletions causing mutations typically involve very large segments of DNA.

<p>False (B)</p> Signup and view all the answers

Point mutations in the untranslated regions of mRNA can significantly alter protein production levels.

<p>True (A)</p> Signup and view all the answers

Alternative donor or acceptor sites created by intron base substitutions are beneficial for normal RNA splicing.

<p>False (B)</p> Signup and view all the answers

Substantial segments of genes can be deleted, inverted, or duplicated without any noticeable effects on the organism.

<p>False (B)</p> Signup and view all the answers

Southern blotting is primarily used to detect small nucleotide changes in DNA sequences.

<p>False (B)</p> Signup and view all the answers

Frameshift mutations can lead to the production of completely different proteins by altering the downstream reading frame.

<p>True (A)</p> Signup and view all the answers

Nucleotide substitutions can occur without any effect on RNA splicing.

<p>True (A)</p> Signup and view all the answers

Polymorphisms occur in randomly chosen segments of human DNA approximately 1000 bp in length with an average of one base pair difference between homologous chromosomes inherited from unrelated parents.

<p>True (A)</p> Signup and view all the answers

Chromosome mutations involve alterations that affect only single nucleotides without changing the overall structure of the chromosomes.

<p>False (B)</p> Signup and view all the answers

Regional mutations can involve changes in the copy number of subchromosomal segments, affecting large sections of chromosomes.

<p>True (A)</p> Signup and view all the answers

Most sequence polymorphisms have significant consequences on gene functioning.

<p>False (B)</p> Signup and view all the answers

The assessment of whether a variant is a polymorphism is based solely on its frequency in a population, needing to exceed 1% of alleles.

<p>True (A)</p> Signup and view all the answers

Nucleotide substitutions are the only type of mutation that can affect the coding sequence of genes.

<p>False (B)</p> Signup and view all the answers

Polymorphisms can be useful as markers for tracking inheritance in genetic studies.

<p>True (A)</p> Signup and view all the answers

Gene or DNA mutations can involve alterations in DNA sequences that range from a single nucleotide up to approximately 100 kb.

<p>True (A)</p> Signup and view all the answers

The concept of genetic polymorphism does not take into consideration the demonstrable effects on the individual.

<p>True (A)</p> Signup and view all the answers

Increased mutation rates have no established link to human diseases.

<p>False (B)</p> Signup and view all the answers

Flashcards

Missense Mutation

A single nucleotide substitution in a gene that changes an amino acid in the protein.

Nonsense Mutation

A single nucleotide substitution that creates a premature stop codon in a gene, stopping protein synthesis.

Silent Mutation

A single nucleotide substitution in a gene that does not change the amino acid in the protein.

Point Mutation

A mutation affecting only one nucleotide base position.

Signup and view all the flashcards

Nucleotide Substitution

A type of mutation where one nucleotide is replaced by another.

Signup and view all the flashcards

Frameshift Mutation

A mutation caused by a deletion or insertion of a number of nucleotides, causing a shift in the reading frame.

Signup and view all the flashcards

Stop Codon

A codon that signals the end of protein synthesis.

Signup and view all the flashcards

Gene Deletion

A mutation involving the loss of a segment of a gene.

Signup and view all the flashcards

Transition mutation

A type of nucleotide substitution where a purine is replaced by another purine (A<->G) or a pyrimidine is replaced by another pyrimidine (C<->T).

Signup and view all the flashcards

Transversion mutation

A type of nucleotide substitution where a purine is replaced by a pyrimidine (A<->C or A<->T or G<->C or G<->T) or vice versa.

Signup and view all the flashcards

Why are transitions more common than transversions?

Because each nucleotide can undergo two transversions but only one transition. However, some mutational processes preferentially cause transitions, leading to their higher prevalence.

Signup and view all the flashcards

5-methylcytosine

A modified form of cytosine where a methyl group is attached. It is found frequently in DNA, particularly in CG dinucleotides.

Signup and view all the flashcards

Deamination

The removal of an amine group from a molecule. In DNA, deamination of 5-methylcytosine leads to thymine.

Signup and view all the flashcards

C>T transition

A common type of mutation in the human genome caused by the spontaneous deamination of 5-methylcytosine, leading to the replacement of cytosine with thymine.

Signup and view all the flashcards

CG dinucleotide

A sequence of two nucleotides, cytosine followed by guanine, which is known as a 'hotspot' for mutations.

Signup and view all the flashcards

Rate of DNA mutations

The frequency at which new mutations arise in a genome. It is estimated to be around 1.2 × 10−8 mutations per base pair per generation.

Signup and view all the flashcards

How many new mutations in each person?

On average, a person receives around 75 new mutations from their parents.

Signup and view all the flashcards

Factors affecting mutation rate

The rate of new mutations can vary between different genes, populations, and even individuals.

Signup and view all the flashcards

Initiator AUG Codon

The start codon that signals the beginning of protein synthesis, coding for the amino acid methionine.

Signup and view all the flashcards

RNA Processing

The series of modifications that convert initial RNA transcripts into mature mRNAs, including capping, polyadenylation, and splicing.

Signup and view all the flashcards

Capping

Adding a protective cap to the 5' end of an mRNA molecule, enhancing its stability and translation efficiency.

Signup and view all the flashcards

Polyadenylation

Adding a tail of adenine nucleotides (poly(A) tail) to the 3' end of an mRNA molecule, protecting it from degradation and aiding in translation.

Signup and view all the flashcards

Splicing

The process of removing introns (non-coding regions) from pre-mRNA and joining exons (coding regions) together to form a mature mRNA.

Signup and view all the flashcards

Splice Donor Site

A specific nucleotide sequence at the 5' end of an intron that signals where splicing should begin.

Signup and view all the flashcards

Splice Acceptor Site

A specific nucleotide sequence at the 3' end of an intron that signals where splicing should end.

Signup and view all the flashcards

Intron

Non-coding regions within a gene that are removed during RNA splicing.

Signup and view all the flashcards

Exon

Coding regions within a gene that are joined together after splicing to form a mature mRNA.

Signup and view all the flashcards

Chromosome Mutation

A mutation that changes the number of chromosomes in a cell.

Signup and view all the flashcards

Regional Mutation

A mutation that affects a portion of a chromosome, possibly altering the copy number of a segment or rearranging its structure.

Signup and view all the flashcards

Gene Mutation

A mutation that alters the DNA sequence, involving insertions, deletions, or substitutions of nucleotides.

Signup and view all the flashcards

SNP (Single Nucleotide Polymorphism)

A variation in a single nucleotide base within a DNA sequence.

Signup and view all the flashcards

Genetic Polymorphism

A variation in a gene's sequence that occurs in more than 1% of a population.

Signup and view all the flashcards

Allelic Variants

Different forms of a gene.

Signup and view all the flashcards

How do SNPs contribute to Genetic Polymorphism?

SNPs are a major source of genetic variation, leading to different alleles of genes.

Signup and view all the flashcards

SNPs and Human Traits

SNPs can influence various human traits, including predisposition to diseases and response to medications.

Signup and view all the flashcards

How are SNPs useful in genetics?

SNPs serve as markers to track inheritance patterns of genes and genomic regions across families and populations.

Signup and view all the flashcards

Polymorphism Applications

Polymorphisms are essential tools in research and clinical practice for studying human genetics and understanding diseases.

Signup and view all the flashcards

Nonhomologous End Joining

A DNA repair process where two broken ends of DNA are joined together without the need for homologous sequences. This is a less accurate repair mechanism compared to homologous recombination, but it is essential in preventing the loss of genetic material.

Signup and view all the flashcards

Gene Mutations: DNA Replication Errors

Mistakes made during the process of DNA replication can lead to gene mutations. These errors occur when the wrong nucleotide is incorporated into the newly synthesized DNA strand.

Signup and view all the flashcards

Gene Mutations: DNA Damage

DNA damage caused by factors like chemicals or radiation can also result in gene mutations. If the damage is not repaired correctly, the DNA sequence might be altered, leading to a mutation.

Signup and view all the flashcards

Proofreading in DNA Replication

A corrective mechanism that acts during DNA replication to identify and fix errors. It involves enzymes that recognize and remove mismatched nucleotides, ensuring that the newly synthesized DNA is as accurate as possible.

Signup and view all the flashcards

DNA Repair Mechanisms

The process of fixing damaged DNA. Different mechanisms are used to identify, remove, and replace damaged nucleotides, protecting the integrity of the genetic code.

Signup and view all the flashcards

Study Notes

Human Genetics Diversity: Mutation and Polymorphism

  • The study of genetic and genomic variation is crucial in medicine and human genetics.
  • Evolution's steady influx of nucleotide variation ensures high genetic diversity and individuality. This applies across human and medical genetics.
  • Genetic diversity includes variations in genome organization, nucleotide sequence changes, copy numbers of DNA segments, protein structure/amount variations in tissues, and clinical disease contexts.

Genetic Diversity

  • Variation exists in the organization of the genome
  • Variations in the nucleotide sequence of the genome
  • Variations in the copy number of large genomic DNA segments
  • Variations in the structure or amount of proteins found in different tissues
  • Any variation in the context of clinical disease

The Sequence of Nuclear DNA

  • The sequence of nuclear DNA is approximately 99.5% identical between unrelated humans.
  • Most DNA sequence differences have little to no effect on appearance, while others directly cause disease.

The Nature of Genetic Variation

  • Alleles are alternative versions of DNA sequence at a particular locus.
  • Many genes have a single predominant allele (wild-type/common allele) present in more than half of a population.
  • Variant/mutant alleles differ from the wild-type due to mutations (permanent changes in DNA sequence or arrangement).
  • Mutations refer to DNA changes but not the individuals carrying the mutated alleles.

Polymorphism

  • A locus exhibiting polymorphism has two or more relatively common alleles (defined as > 1% frequency) in a population.
  • Most variant alleles are infrequent enough to not qualify as polymorphisms. Some are extremely rare ("private alleles").

The Concept of Mutation

  • A study of mutations begins with single nucleotide changes up to entire chromosome alterations.

Useful Databases

Mutations at Three Different Levels

  • Chromosome mutations change chromosome numbers in a cell
  • Subchromosomal/regional mutations change parts of a chromosome (copy number changes, rearrangements).
  • Gene/DNA mutations alter DNA sequence (substitutions, deletions, insertions).

The Concept of Genetic Polymorphism

  • A randomly chosen 1000 bp segment of human DNA typically has only one base pair difference between homologous chromosomes (unrelated parents).
  • Whether a variant is a polymorphism depends on its frequency (>1% in a population), not the type of mutation, size of the mutated segment, or effect on the individual.

Polymorphisms Located

  • Most sequence polymorphisms are located between genes or within introns and are insignificant to gene function.
  • Some reside in protein-coding regions, leading to different protein variants and human population differences.
  • Others are regulatory regions, having vital effects on transcription or RNA stability.

Polymorphisms as Tools

  • Polymorphisms are crucial for human and medical genetics.
  • Identifying different inherited gene forms/genome segments provide tools for research and clinical application.
  • Polymorphisms are used in research (mapping genes, linkage analysis, disease detection), prenatal diagnostics, genetic disease carriers, blood banking/organ transplantation, forensic applications (paternity, victim identification, suspect matching).

Inherited Variation and Polymorphism in DNA

  • The Human Genome Project (and related studies) yields comprehensive DNA sequence information.
  • This data allows characterization of types and frequencies of polymorphic variation in the human genome.
  • DNA polymorphism classification based on DNA sequence variations between alleles.

Types of Variation in the Human Genome

  • Single nucleotide polymorphism (SNP): usually two alleles differing by a single nucleotide; common, often every 1000 bp.
  • Insertion/deletions (indels): 2-100 nucleotides; number in hundreds of thousands; simple (two alleles) or multiallelic (variable number of repeated segments).
  • Microsatellites (STRPs): repeats of short tandem nucleotide sequences (2-4 bp); many alleles; readily determined by PCR.
  • Minisatellites (VNTRs): repeats of longer tandem sequences; many alleles; used for DNA fingerprinting.
  • Mobile element insertion polymorphisms: insertion of mobile genetic elements. Common Alu and LINE families.
  • Copy number variants (CNVs): variation in the number of copies of larger segments (200 base pairs - 2 megabases.)

Microsatellites

  • Repeats of di-, tri-, or tetra-nucleotide sequences (e.g. TGTG, CAACAA).
  • Allele differences due to variations in repeat number, thus called short tandem repeat polymorphisms or STRPs.

Minisatellites

  • Repeated nucleotide sequences 10–100 bp in length.
  • Variation in the number of repeats causes different alleles.

Mobile Element Insertion Polymorphisms

  • Mobile genetic elements (Alu, LINE families) form nearly half of the human genome.
  • These repetitive sequences can affect gene function.

Copy Number Polymorphisms (CNVs)

  • Variations in the number of larger DNA segments within a genome (200bp to 2 Mb).
  • Can have two alleles or multiple alleles (different copy numbers).
  • Detected currently by comparative genome hybridization.

Inversion Polymorphisms

  • Inversions involve inverting a DNA segment within a chromosome.
  • In their balanced form, have little effect but homologous recombination can cause deletion/duplication of linked regions.

Origins and Frequency of Mutation Types

  • Mutations arise during DNA replication, repair, recombination, cell division.
  • Mutation frequency per locus per cell division (genome/chromosome) is a measure of error proneness, but is less significant for medical geneticists than mutation frequency per locus per generation.

Categories of Human Mutation (Based on a table provided)

  • Genome mutations: arise from chromosome missegregation.
  • Chromosome mutations: arise from chromosome rearrangements.
  • Gene mutations: caused by base pair mutations.

Mutation Consequences (based on a tabular presentation):

  • Nucleotide Substitutions broadly include missense, nonsense, silent, frame shift mutations, etc.
  • Deletions and Insertions include a broad spectrum of indels, insertions, deletions including larger scale rearrangements of genes.

DNA Replication Errors

  • Most replication errors are promptly corrected (proofreading) by DNA repair enzymes.
  • Despite this, a small number of errors occur; estimated one mutation of a base pair per 10^10 per cell division in humans).

Repair of DNA Damage

  • Spontaneous chemical processes can damage nucleotides.
  • Repair mechanisms may introduce errors during the repair process.
  • Damage/repair processes are a major source of permanent mutations.

Hotspot Mutations

  • Transition mutations (i.e A-G substitutions) are more common than transversions.
  • Spontaneously occurring deamination of methylcytosine is responsible for the high frequency of C-T transitions (methyl-CG is a hotspot).

Sex Differences in Mutation Rates

  • New mutations occur in germline during mitotic and meiotic divisions in gametogenesis (spermatogenesis and oogenesis).
  • Female gametes (oogenesis): oocytes in meiosis develop before birth; they remain there until ovulation; more susceptible to mutations due to extended duration.
  • Male gametes (spermatogenesis): continuous processes throughout life; thus more divisions mean higher exposure to mutations

Variation in Individual Genomes

  • Large-scale genome sequencing helps track amount and type of variation expected in individual genomes.
  • Tens of thousands of human genomes are now sequenced, providing insights into genetic diversity and disease.

Variation Detected in a Typical Human Genome

  • Provides an array of mutations in typical human genomes. (5-10 million SNPs, 25,000–50,000 rare variants, 75 new base pair mutations, 3-7 CNVs, 200,000-500,000 indels, 200-250 frameshift and more)

Clinical Sequencing Studies

  • Determining the extent of genome variation (sequence/expression) impacting disease onset/progression is needed for genomic medicine.
  • Genomes influence various aspects in the natural history of disease and management.

Sequencing Studies Target

  • Whole-genome and whole-exome sequencing assists in identifying de novo mutations causing certain conditions (e.g. autism, schizophrenia, intellectual disability).
  • Clinical studies may target germline or somatic variants in the context of cancer.

Other Important Concepts

  • Regional Mutations: mutations affecting genome structure due to homologous recombination between similar sequences, or spontaneous DNA breaks.
  • Dynamic Mutations: these mutations involve repeated nucleotide sequences, and repeat expansion during gametogenesis may drive disease, through interference with RNA processes.

Studying That Suits You

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

Quiz Team

Related Documents

Description

Explore the different types of genetic mutations and their implications on protein encoding. This quiz covers missense, nonsense, silent, and dynamic mutations, along with the concept of mutation hotspots and DNA repair mechanisms. Test your understanding of how these mutations contribute to genetic diseases.

More Like This

Use Quizgecko on...
Browser
Open
Browser
Browser