Comprehensive Genetics Exam 2 Study Guide

Chromosomal Abnormalities

Numerical Chromosomal Abnormalities

Chromosomal numerical abnormalities involve changes in the number of chromosomes, which can have significant effects on development and viability in humans.

• Aneuploidy: The presence of an abnormal number of chromosomes in a cell (e.g., trisomy, monosomy).

• Common Types: Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), Trisomy 13 (Patau syndrome), and sex chromosome aneuploidies (e.g., XO, XXY, XYY, XXX).

• Compatibility with Life: Some aneuploidies, such as Trisomy 21 and certain sex chromosome aneuploidies, are compatible with birth and survival to adulthood, while others are typically lethal.

Structural Chromosomal Abnormalities

Structural abnormalities involve changes in the arrangement of genetic material within or between chromosomes.

• Reciprocal Translocations: Exchange of segments between non-homologous chromosomes.

• Insertional Translocations: A segment from one chromosome is inserted into another chromosome.

• Robertsonian Translocations: Fusion of two acrocentric chromosomes at their centromeres.

• Insertions, Deletions, Duplications, Inversions: Gain, loss, or rearrangement of chromosomal segments.

Sex Chromosome Aneuploidies

Common Human Sex Chromosome Aneuploidies

• XO (Turner Syndrome): Female with only one X chromosome.

• XXY (Klinefelter Syndrome): Male with an extra X chromosome.

• XYY: Male with an extra Y chromosome.

• XXX: Female with an extra X chromosome.

Historical Discoveries in DNA Structure and Function

Key Scientists and Their Contributions

• Miescher: Discovered nuclein (DNA) in cell nuclei.

• Flemming: Described mitosis and chromatin.

• Fol & Hertwig: Observed fertilization and chromosome behavior.

• Levene: Identified nucleotide structure.

• Griffith: Demonstrated transformation in bacteria.

• Garrod: Studied inborn errors of metabolism.

• Avery, MacLeod & McCarty: Identified DNA as the transforming principle.

• Hershey & Chase: Confirmed DNA as genetic material using bacteriophages.

• Meselson & Stahl: Demonstrated semiconservative DNA replication.

• Chargaff: Established base pairing rules (A=T, G=C).

• Sister Miriam Stimson, Franklin & Gosling: Provided X-ray diffraction images of DNA.

• Watson & Crick: Proposed the double helix model of DNA.

• Nirenberg & Matthaei: Deciphered the genetic code.

• Mullis: Invented PCR (polymerase chain reaction).

• Palade: Discovered ribosomes.

• Jacob & Monod: Described gene regulation in bacteria (lac operon).

• Har Gobind Khorana, Holley, Crick, Brenner & Pardee: Contributed to understanding the genetic code and gene expression.

Nucleic Acids: DNA and RNA

Five Nucleotides in DNA & RNA

• DNA: Adenine (A), Guanine (G), Cytosine (C), Thymine (T)

• RNA: Adenine (A), Guanine (G), Cytosine (C), Uracil (U)

Similarities and Differences Between DNA and RNA

• Similarities: Both are polymers of nucleotides, contain A, G, C, and a pentose sugar-phosphate backbone.

• Differences: DNA contains deoxyribose and thymine; RNA contains ribose and uracil. DNA is usually double-stranded; RNA is usually single-stranded.

Central Dogma of Molecular Biology

The central dogma, as outlined by Francis Crick in 1958, describes the flow of genetic information:

• DNA → RNA → Protein

DNA Structure and Replication

Structural Features of DNA (B-form)

• Double helix with antiparallel strands

• Major and minor grooves

• Base pairing: A-T (2 H-bonds), G-C (3 H-bonds)

• Right-handed helix

ATP and DNA Replication

• ATP provides energy for DNA synthesis by donating phosphate groups during nucleotide addition.

Replication in Prokaryotes vs Eukaryotes

• Prokaryotes: Single origin of replication, circular DNA, fewer proteins involved.

• Eukaryotes: Multiple origins, linear chromosomes, complex machinery, telomere replication issues.

Topoisomerase and Gyrase

• Topoisomerase: Relieves supercoiling during DNA replication.

• Gyrase: A type of topoisomerase found in bacteria, introduces negative supercoils.

DNA Polymerase: Structural Features

• Palm: Catalytic site for nucleotide addition.

• Fingers: Position incoming nucleotides.

• Thumb: Holds DNA in place during synthesis.

Exonucleases vs Endonucleases

• Exonucleases: Remove nucleotides from the ends of DNA.

• Endonucleases: Cut DNA at internal sites.

Transcription and RNA Processing

Major Classes of RNA Molecules

• mRNA: Messenger RNA, encodes proteins.

• tRNA: Transfer RNA, brings amino acids to ribosome.

• rRNA: Ribosomal RNA, forms ribosomes.

• snRNA, miRNA, siRNA: Regulatory and processing roles.

Promoters in Prokaryotes and Eukaryotes

• Bacterial Promoters: Contain -10 (Pribnow box) and -35 consensus sequences.

• Eukaryotic Core Promoters: TATA box, Inr (initiator), BRE, DPE elements.

Initiation of Transcription

• RNA polymerase binds promoter, forms open complex.

• Abortive initiation: Short transcripts are made and released.

• Promoter escape: RNA polymerase clears the promoter and elongation begins.

RNA Processing in Eukaryotes

• 5' capping, 3' polyadenylation, splicing of introns.

Translation and Protein Synthesis

tRNA Charging

• Aminoacyl-tRNA synthetase attaches specific amino acid to tRNA.

Translation Process

• Initiation, elongation, and termination phases.

• EPA sites: Entry (A), Peptidyl (P), Exit (E) sites on ribosome.

Genetic Code and Mutations

• Silent Mutation: No change in amino acid.

• Missense Mutation: Changes one amino acid.

• Nonsense Mutation: Introduces a stop codon.

• Frameshift Mutation: Alters reading frame by insertion/deletion.

DNA Damage and Repair

Types of DNA Damage

• Depurination, deamination, thymine dimers, double-strand breaks.

• Caused by UV light, chemicals, radiation, metabolic byproducts.

DNA Repair Mechanisms

• Direct repair, base excision repair, nucleotide excision repair, mismatch repair, homologous recombination, non-homologous end joining.

Epigenetics

Major Classes and Effects

• DNA Methylation: Addition of methyl groups to DNA, often silences genes.

• Histone Modification: Acetylation, methylation, phosphorylation alter chromatin structure and gene expression.

• Non-coding RNAs: Regulate gene expression post-transcriptionally.

Epigenetic traits can be inherited during cell division and sometimes across generations.

Summary Table: Types of Mutations and Their Effects

Mutation Type	Definition	Effect on Protein
Silent	Base change, no amino acid change	No effect
Missense	Base change, different amino acid	May alter function
Nonsense	Base change, introduces stop codon	Truncated protein
Frameshift	Insertion/deletion, shifts reading frame	Usually nonfunctional protein

Summary Table: DNA Repair Mechanisms

Repair Mechanism	Type of Damage Repaired
Direct Repair	Specific chemical modifications (e.g., thymine dimers)
Base Excision Repair	Small, non-helix-distorting base lesions
Nucleotide Excision Repair	Bulky, helix-distorting lesions
Mismatch Repair	Replication errors (mismatched bases)
Homologous Recombination	Double-strand breaks
Non-homologous End Joining	Double-strand breaks

Additional info: These notes synthesize and expand upon the study guide topics, providing definitions, examples, and context for exam preparation. For diagrams such as replication forks, tRNA structure, and consensus sequences, refer to your textbook or lecture slides for visual reinforcement.