ABPath Molecular Genetic Pathology study guide
ABPath Molecular Genetic Pathology · Work through your exam, one topic at a time.
Molecular Genetic Pathology (MGP) is an ABPath subspecialty certification examination, offered in cooperation with the American Board of Medical Genetics and Genomics, for pathologists who want formal recognition of subspecialty expertise in molecular diagnostics. It is a one-day, computer-based exam that combines written and practical questions in each section, and every item is multiple-choice in the one-best answer format. The ABPath Molecular Genetic Pathology study guide has 8 sections and about 3,391 words.
01Normal Structure and Function of the Genome
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.
306 words, about 2 min02Molecular Techniques and Methods
Know the principle, strengths, limitations, and failure modes of each platform. PCR and real-time PCR (threshold cycle, melt curve, efficiency), Sanger sequencing (chain termination, dideoxynucleotides, ~700-1000 bp reads), next-generation sequencing (clonal amplification, massively parallel short reads, depth and coverage), and long-read platforms.
308 words, about 2 min03Human Genetic Principles: DNA/RNA Structure, Mutation Types, and Nomenclature
Understand the classes of genetic variation: single-nucleotide variants (substitutions), small insertions/deletions, copy-number variants, structural variants, and repeat expansions. Distinguish synonymous, missense, nonsense, frameshift, splice-site, and regulatory variants, and know predicted consequences (loss of function, gain of function, dominant-negative).
308 words, about 2 min04Gene Structure and Function
Know the anatomy of a eukaryotic gene: promoter and core elements, 5' UTR, exons and introns with canonical splice sites (GT-AG rule), branch point, 3' splice site, and 3' UTR with polyadenylation signal. Understand alternative splicing, alternative promoters, and tissue-specific expression, plus noncoding RNAs and their regulatory roles.
284 words, about 1 min05Population Genetics and Risk Calculation
Understand Hardy-Weinberg equilibrium: p + q = 1 and p^2 + 2pq + q^2 = 1, where p and q are allele frequencies. Know how to calculate carrier frequency from disease incidence for autosomal recessive conditions (carrier frequency ~2 x sqrt(incidence)).
291 words, about 1 min06Quality Improvement, Quality Control, Quality Assurance, and Ethical/Legal/Regulatory Issues
Distinguish quality control (QC, the assay-level checks run with each batch: positive and negative controls, calibration, precision), quality assurance (QA, the broader program including proficiency testing, audits, and documentation), and quality improvement (QI, systematic process improvement such as PDSA cycles and root-cause analysis). Know the regulatory framework: CLIA certification, CAP accreditation, FDA oversight of laboratory-developed tests, and the role of the Clinical Laboratory Improvement Amendments in test validation.
293 words, about 1 min07Inherited Disorders: Single-Gene, Multigenic, and Mitochondrial
Know the major inheritance patterns and representative disorders: autosomal dominant (Huntington disease, Marfan syndrome, familial hypercholesterolemia), autosomal recessive (cystic fibrosis, sickle cell disease, phenylketonuria), X-linked (Duchenne muscular dystrophy, hemophilia, Fragile X), imprinting (Prader-Willi/Angelman), and mitochondrial (MELAS, MERRF, Leber hereditary optic neuropathy). Understand trinucleotide repeat disorders and anticipation, and the concept of penetrance and variable expressivity.
263 words, about 1 min08Neoplastic Diseases and Other Acquired Disorders
Understand the molecular hallmarks of cancer: oncogene activation (KRAS, EGFR, BRAF, MYC), tumor suppressor loss (TP53, RB1, APC, PTEN), and DNA repair defects (mismatch repair, homologous recombination, BRCA1/2). Know the difference between driver and passenger mutations, clonal evolution, and the role of tumor heterogeneity.
1,338 words, about 7 min