ABPath Molecular Genetic Pathology study materials
ABPath Molecular Genetic Pathology study resources

ABPath Molecular Genetic Pathology: Normal Structure and Function of the Genome

ABPath Molecular Genetic Pathology · Work through your exam, one topic at a time.

All guide sections

Normal Structure and Function of the Genome

Core concepts

A candidate must be fluent in the architecture of DNA and chromatin: nucleotide chemistry, the antiparallel double helix, base-pairing rules, major and minor grooves, and the packaging hierarchy from nucleosome (146 bp around an H2A/H2B/H3/H4 octamer) to 30-nm fiber to loop domains to chromosome. Know the distinction between euchromatin and constitutive versus facultative heterochromatin, and the role of histone modification and DNA methylation in gene regulation.

Be able to describe the central dogma with precision: replication (semiconservative, leading/lagging strands, proofreading), transcription (promoter, TATA box, enhancers, silencers, transcription factors), RNA processing (5' cap, splicing, polyadenylation), and translation (codons, tRNA, ribosome). Know the genetic code and its degeneracy, the start codon AUG (methionine) and the stop codons UAA, UAG, UGA.

Traps

Questions often test the directionality of synthesis (DNA and RNA polymerases both synthesize 5' to 3'; the lagging strand is made in Okazaki fragments), the difference between coding and template strands, and the fact that mitochondrial DNA is circular, maternally inherited, and uses a slightly altered genetic code. Do not confuse chromatin remodeling with sequence mutation.

Rule of thumb

For any "where does this happen" question, anchor to compartment: replication and transcription in the nucleus (transcription and translation coupled in prokaryotes only), splicing in the nucleus, translation in the cytoplasm; mitochondrial genes use their own machinery.

Worked example

A question asks how many nucleotides encode a 100-amino-acid protein excluding the stop codon: 100 x 3 = 300 nucleotides of coding sequence, and remember the stop codon adds three more.