Genetics Day 1

Questions and Answers

What genetic risk is associated with the patient from the genetic testing?

Cystic fibrosis

Emphysema (correct)

Huntington's disease

Hemophilia

What lifestyle factor is noted regarding the patient?

He has never smoked.

He smokes cigars. (correct)

He exercises frequently.

He is a vegetarian.

Why might the patient be reluctant to share genetic information with his wife?

He thinks the information is not important.

He is unsure how she will react. (correct)

He is not concerned about the risks.

He believes the tests are unreliable.

Which condition is NOT mentioned as a potential risk from the genetic testing?

Diabetes Signup and view all the answers

What is a possible consequence of the patient being overweight?

Increased risk of colon cancer Signup and view all the answers

Which of the following best describes the patient's overall health condition?

He is relatively healthy but has some risk factors. Signup and view all the answers

What encompasses the details of ancestry and predictions of future health?

Your genome Signup and view all the answers

What proportion of the human genome is made up of protein coding sequences?

1.5% Signup and view all the answers

From where is mitochondrial DNA inherited?

Only from the mother Signup and view all the answers

What is the estimated number of genes in the human genome?

25,000 Signup and view all the answers

What characterizes tolerated SNPs?

They are found in non-coding regions. Signup and view all the answers

Which method is used to identify SNP variations?

Amplifying and hybridizing DNA probes. Signup and view all the answers

Which organ is most commonly affected by mitochondrial DNA-related diseases?

Skeletal muscle Signup and view all the answers

What is the size of the human mitochondrial genome?

16.5 kb Signup and view all the answers

What was the cost and coverage of sequencing the human genome in 2024?

$500 with 30-50x coverage. Signup and view all the answers

Which population groups were identified using genome-wide SNPs from Qatari genomes?

Q1 Arab, Q2 Persian, Q3 African. Signup and view all the answers

What percentage of human genetic diseases is attributed to mitochondrial DNA?

1% Signup and view all the answers

What role do genes play in cellular function?

Tell cells how to function Signup and view all the answers

What do copy number variations (CNVs) include?

Insertions and deletions of DNA segments. Signup and view all the answers

How does inbreeding in the Qatari population compare to that in European populations?

Qataris have a lower inbreeding coefficient. Signup and view all the answers

What is the role of promoters in gene expression?

They control which genes are expressed in specific tissues. Signup and view all the answers

What percentage of DNA sequences do unrelated humans share?

99.9% Signup and view all the answers

What is a primary contributor to human heterozygosity?

Single nucleotide polymorphisms (SNPs) Signup and view all the answers

How many known variant sites are there in the NCBI database?

40 million Signup and view all the answers

What process results in thousands of different protein types from genes?

Alternative splicing Signup and view all the answers

What is a SNP?

A variant of a single nucleotide Signup and view all the answers

What are copy number variants?

Variants of 1 kb to several Mb in length Signup and view all the answers

What do epigenetic controls like methylation do?

They can turn genes on and off. Signup and view all the answers

What type of genetic variation includes whole chromosomes?

Chromosomal variants Signup and view all the answers

What is the significance of histone modifications in gene regulation?

They influence the physical structure of DNA. Signup and view all the answers

What is the probability that the woman is a heterozygous carrier for a cystic fibrosis mutation?

1/2 Signup and view all the answers

What is the probability that a child will be affected with Phenylketonuria PKU if his/her mother is a heterozygous carrier?

1/256 Signup and view all the answers

If persons III-1 and III-2 mate, what is the probability that their offspring will be affected by PKU?

1/36 Signup and view all the answers

What type of inheritance does Phenylketonuria (PKU) follow?

Autosomal recessive Signup and view all the answers

What consequence does untreated PKU have on affected children?

Severe mental retardation Signup and view all the answers

Assuming II-1 and II-5 are homozygous normal, which genetic state influences III-1 and III-2's offspring?

Both being heterozygous Signup and view all the answers

How many ways can the offspring inherit a recessive disorder from heterozygous parents?

4 Signup and view all the answers

In a pedigree analysis, which individual is affected by PKU?

II-3 Signup and view all the answers

What does a heterozygous state indicate about an individual concerning autosomal recessive disorders?

They are a carrier for the disorder Signup and view all the answers

What component in genetics is essential for calculating the probability of inheriting a recessive disorder?

Parental genotype Signup and view all the answers

What forms the base pairing in DNA according to Watson-Crick model?

Adenine pairs with Thymine Signup and view all the answers

Which of the following statements about DNA base pairing is correct?

Guanine and Cytosine form three hydrogen bonds Signup and view all the answers

What does Chargaff’s rule state regarding DNA composition?

A + G = T + C Signup and view all the answers

What element is consistently found in the structure of DNA bases?

Nitrogen Signup and view all the answers

Which pair characterizes the structure of DNA based on base pairing principles?

Purine with Pyrimidine Signup and view all the answers

Who are credited with the development of the molecular model of DNA?

James Watson and Francis Crick Signup and view all the answers

What is the role of methyl guanine methyl transferase (MGMT)?

To reverse the methylation of guanine bases Signup and view all the answers

Which type of repair does base excision repair (BER) primarily target?

Damage caused by endogenous events Signup and view all the answers

What is a disadvantage of base excision repair (BER)?

It involves a complex mechanism of action Signup and view all the answers

Which of the following functions does nucleotide excision repair (NER) serve?

Repair of DNA distortions caused by bulky adducts Signup and view all the answers

What process allows the generation of multiple peptides from the same mRNA due to the use of different start codons?

Leaky scanning Signup and view all the answers

Which elongation factor is responsible for translation accuracy in prokaryotes?

EF-Tu Signup and view all the answers

What process does base excision repair (BER) NOT include?

Incorporation of new nucleotides Signup and view all the answers

What enzyme system is associated with nucleotide excision repair (NER) in prokaryotes?

Uvr excinuclease system Signup and view all the answers

What mechanism allows for fast protein synthesis by coupling GTP hydrolysis?

Codon-anticodon interaction Signup and view all the answers

What phenomenon occurs when tRNA slips on the ribosome leading to a frameshift?

tRNA slippage Signup and view all the answers

Which bases are typically recognized by base-specific DNA glycosylases in BER?

8-oxoguanine and uracil Signup and view all the answers

How many amino acids can eukaryotic ribosomes incorporate per second during protein synthesis?

2-6 Signup and view all the answers

What is a key mechanism involved in base excision repair (BER)?

Base flipping mechanism Signup and view all the answers

What is the primary role of recycling factors in translation termination?

To prevent initiation on downstream start codons Signup and view all the answers

What is the primary role of messenger RNA (mRNA) in the process of transcription?

To carry coded information from DNA to ribosomes Signup and view all the answers

What distinguishes RNA from DNA chemically?

RNA uses uracil instead of thymine Signup and view all the answers

Which event occurs during transcription?

RNA is synthesized from a DNA template Signup and view all the answers

How does co-transcriptional translation occur in cells?

RNA is translated before transcription is complete Signup and view all the answers

Which of the following accurately describes RNA’s typical structural form?

RNA is usually found as a single-stranded molecule Signup and view all the answers

What is the primary function of ribosomal RNA (rRNA)?

To catalyze the formation of peptide bonds Signup and view all the answers

During RNA processing, what is the significance of RNA splicing?

To remove introns from the pre-mRNA molecule Signup and view all the answers

What is the process of transcription primarily concerned with?

Synthesis of RNA from DNA Signup and view all the answers

Which component is essential for the synthesis of RNA during transcription?

DNA template Signup and view all the answers

Which of these components is NOT involved in the transcription process?

Transfer RNA (tRNA) Signup and view all the answers

Study Notes

Case Overview

35-year-old investment banker with routine health examination, presenting no significant health issues.
Lifestyle factors: cigar smoking, 15 lbs overweight, infrequent exercise.
Engaged in genetic testing through a saliva sample for predictive analysis.

Consumer Predictive Genetic Testing

Identified increased risk for several conditions:
- Emphysema
- Coronary artery disease
- Allergy to penicillin-type antibiotics
- Colon cancer
- Early onset Alzheimer's
Patient expresses concern about sharing genetic information with wife and seeks guidance.

Importance of Patient’s Genome

Patient's genome reveals ancestry and potential health risks.
Mutations may indicate possible diseases and responses to treatments, diet, and medications.
The genome acts as a guide for disease prevention and healthcare customization.

Human Nuclear Genome

Composed of approximately 3.1 billion DNA letters across 2 sets of 23 chromosomes from each parent.
Encodes about 25,000 genes responsible for cellular functioning.
Protein-coding sequences constitute only 1.5% of the entire genome.

Mitochondrial Genome

Contains 16.5 kb of DNA, encoding essential components for oxidative phosphorylation and protein synthesis.
Inherited exclusively from the mother and linked to ~1% of genetic diseases, affecting high-energy-use organs.

Gene Counting and Expression

Estimated 25,000 genes contribute to human traits.
Various mechanisms such as epigenetics and alternative splicing enable diverse protein production.
Promoters and regulatory elements influence gene expression in specific tissues.

Genetic Diversity

Unrelated humans exhibit 99.9% shared DNA.
Human diversity includes approximately 10 to 15 million single nucleotide polymorphisms (SNPs) arising from evolution.

Single Nucleotide Polymorphisms (SNPs)

Polymorphic variations in DNA sequences potentially affecting protein function.
Two categories:
- Tolerated SNPs: typically do not alter function.
- Deleterious SNPs: can disrupt protein function, impacting health.

Genome Sequencing Costs and Accessibility

Cost of sequencing the human genome has drastically decreased from 2.3billion(2001)toapproximately2.3 billion (2001) to approximately 2.3billion(2001)toapproximately500 (2024).
Advances in technology have reduced the time for sequencing to 1-3 days and increased coverage.

Copy Number Variations (CNVs)

Submicroscopic genetic variations that can influence gene expression and phenotypic outcomes.
CNVs include deletions, insertions, duplications, and other complex changes.

Genetic Variation and Disease Risk

Genetic disorders can be monogenic or complex, involving multiple genes.
Common monogenic disorders include cystic fibrosis and hereditary hemochromatosis.

Modifier Genes

Genes that influence the relationship between other genes and their expression, contributing to phenotype variations.

Complex, Multigenic Disorders

Disorders like cardiovascular diseases, diabetes, and certain cancers arise from the interaction of multiple genes.

Genetic Alleles in Complex Disorders

Low prevalence, high penetrance alleles like BRCA1/2 and HNPCC increase the risk of specific cancers.
High prevalence, low penetrance alleles such as APC and Factor V Leiden can elevate risks for certain health conditions.

Alzheimer’s Disease

Involves both high and low prevalence genetic factors in its manifestation and progression.

Cystic Fibrosis Carrier Probability

Cystic fibrosis (CF) is an autosomal recessive disorder; both parents must carry the mutation for a child to be affected.
Probability of being a carrier for a woman with a niece affected by CF is 1 in 4, or 25%, assuming the affected niece's parents are both carriers.

Phenylketonuria (PKU) Overview

Phenylketonuria is an autosomal recessive condition characterized by metabolism errors in phenylalanine, leading to severe intellectual disabilities if untreated.
A known heterozygous carrier mother has a probability of 25% for each child to inherit the PKU disorder.

Genetic Probability Calculations

The formula for genetic inheritance probability in autosomal recessive conditions:
- For a mother's heterozygosity (P): 1 (mother) x 1/4 (child probability) = 1/4 chance of child being affected.
Further calculations for different scenarios can yield probabilities such as 1 in 256 for certain offspring combinations.

Pedigree Analysis and Inheritance

Pedigree must be assessed to determine inheritance modes: dominant, recessive, or linked traits.
Affected individuals can be represented; homozygous normal individuals can be assumed based on pedigree notation (e.g., II-1 and II-5).
Example calculations for III-1 and III-2 mating:
- Both heterozygous (1/2 x 1/2) yield a 1/4 chance for affected children, contextualizing genetic ratio implications.

Probability of Offspring Affected

If both III-1 and III-2 are heterozygous carriers, the offspring have a calculated probability of being affected:
- Using the formula 1/4 (affected children probability) x 1/3 (heterozygous probability) results in 1/36 chance for an affected offspring.

Conclusion

Understanding probabilities in genetic counseling is crucial for assessing risks and guiding patients in potential genetic outcomes for their children.

Base Pairing and DNA Structure

Base pairing follows Watson-Crick rules: A pairs with T (2 hydrogen bonds) and G pairs with C (3 hydrogen bonds).
A constant width in DNA is maintained by pairing a purine (A, G) with a pyrimidine (T, C).
Chargaff's rule states that the amount of adenine (A) plus guanine (G) equals thymine (T) plus cytosine (C).
DNA was structurally modeled by James Watson and Francis Crick in 1953.
Methylation of guanine can be reversed by the enzyme MGMT, critical for DNA repair.

DNA Repair Mechanisms

Excision repair types include Base Excision Repair (BER), Nucleotide Excision Repair (NER), and Mismatch Repair (MMR).
BER addresses damage from endogenously occurring events, such as oxidative damage and deaminations.
Key steps in BER include damage recognition, incision, removal, gap filling, and ligation.
BER is energetically inexpensive but requires specificity provided by DNA glycosylases.

Nucleotide Excision Repair (NER)

NER is used for repairing bulky DNA adducts that distort the helix, offering flexibility in response to environmental damage.
In prokaryotes, NER is carried out by the Uvr excinuclease system.

Central Dogma of Molecular Biology

Central dogma describes the flow of genetic information from DNA to RNA to protein.
RNA, differing from DNA by containing ribose sugar and uracil (U) instead of thymine (T), exists as a single strand.
Transcription involves synthesizing mRNA from DNA, while translation converts mRNA to peptides in the cytoplasm.

Transcription and Translation

Transcription occurs in the nucleus, resulting in the formation of mRNA.
Translation involves the decoding of mRNA into polypeptides, utilizing tRNA and ribosomes.
Co-transcriptional translation is observed where translation occurs simultaneously with transcription.

Variability in Translation

Some viruses utilize leaky scanning, tRNA slippage, and other mechanisms to generate multiple peptides from one mRNA strand.
Proofreading during translation is maintained by elongation factors which ensure accuracy by driving the process and hydrolyzing GTP.

Ribosome Function and Antibiotic Interaction

Multiple ribosomes can simultaneously translate a single mRNA (polyribosome) for efficient protein synthesis.
Common antibiotics and toxins target prokaryotic ribosomes, inhibiting processes such as tRNA-mRNA interactions and peptide bond formation:
- Aminoglycosides (e.g., streptomycin) bind to small ribosomal subunits.
- Chloramphenicol inhibits peptide bond formation at the peptidyl transferase center.
- Tetracycline blocks tRNA-mRNA interactions.
- Macrolides bind the large subunit, preventing peptide bond formation.
- Ribosome inactivating proteins like Shigella toxin and ricin disrupt rRNA GTPase interactions.

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