ABPath Molecular Genetic Pathology flashcards

32 cards. Read the term and the definition here. The deck at the top of this page is optional.

Central dogma

The flow of genetic information from DNA to RNA (transcription) to protein (translation); reverse transcription occurs in retroviruses.

Nucleosome composition

147 base pairs of DNA wrapped around an octamer of histone proteins (two each of H2A, H2B, H3, H4).

Sanger sequencing

Chain-termination method using dideoxynucleotides to generate fragments of varying lengths, separated by capillary electrophoresis.

qPCR Ct value

Cycle threshold; the PCR cycle at which fluorescence exceeds background. Inversely proportional to the initial amount of target nucleic acid.

Hardy-Weinberg equation

p² + 2pq + q² = 1; used to calculate genotype frequencies and carrier frequency (2pq) for autosomal recessive disorders.

HGVS nomenclature

Standardized variant naming: c. for coding DNA, g. for genomic, p. for protein; e.g., c.76A>T (p.Lys26*).

CLIA '88

Federal law regulating clinical laboratories; ensures quality standards for testing, including proficiency testing and quality control.

GINA

Genetic Information Nondiscrimination Act; prohibits discrimination in health insurance and employment based on genetic information.

Cystic fibrosis genetics

Autosomal recessive; CFTR mutations (e.g., F508del); carrier frequency ~1/25 in Caucasians; sweat chloride test for diagnosis.

Fragile X syndrome

X-linked dominant; CGG repeat expansion (>200) in FMR1 causing methylation and gene silencing; carrier females may be affected.

BCR-ABL1 fusion

t(9;22) translocation in chronic myeloid leukemia; encodes constitutively active tyrosine kinase; targeted by imatinib.

EGFR TKI resistance

EGFR T790M mutation confers resistance to first-generation tyrosine kinase inhibitors in non-small cell lung cancer; osimertinib is effective.

HIV viral load

Quantitative RT-PCR measurement of HIV RNA copies/mL; used to monitor antiretroviral therapy response and detect virologic failure.

16S rRNA sequencing

Broad-range PCR and sequencing of bacterial 16S ribosomal RNA gene for identification of culture-negative infections.

STR analysis

Short tandem repeat profiling; amplifies polymorphic repeat loci for identity testing, forensics, and chimerism monitoring.

HLA-B*57:01

HLA allele strongly associated with abacavir hypersensitivity; screening is recommended before initiating abacavir therapy.

CYP2D6 ultrarapid metabolizer

Increased conversion of codeine to morphine, leading to risk of toxicity; alternative analgesic recommended.

TPMT deficiency

Reduced thiopurine methyltransferase activity increases risk of severe myelosuppression with azathioprine or mercaptopurine; dose reduction required.

VCF format

Variant Call Format; text file storing sequence variants with genomic position, reference and alternate alleles, and quality metrics.

ACMG variant classification

Five-tier system: pathogenic, likely pathogenic, variant of uncertain significance, likely benign, benign; based on evidence criteria.

Mitochondrial inheritance

Maternal transmission of mtDNA; heteroplasmy and threshold effect determine phenotypic expression of mitochondrial disorders.

JAK2 V617F

Activating mutation in myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, primary myelofibrosis); detected by PCR or sequencing.

MLPA

Multiplex ligation-dependent probe amplification; quantifies exon-level copy number changes for deletions and duplications.

Digital PCR

Partitions sample into thousands of droplets for absolute quantification; detects rare variants at 0.1–0.01% allele frequency.

Heteroplasmy

Coexistence of mutant and wild-type mitochondrial DNA within a cell or tissue; affects phenotype severity.

Imprinting disorders

Prader-Willi (loss of paternal 15q11-q13 expression) and Angelman (loss of maternal UBE3A expression) syndromes.

Proficiency testing

External quality assessment program that evaluates laboratory performance by testing unknown specimens; required for CLIA certification.

HLA typing

High-resolution genotyping of HLA loci (A, B, C, DRB1, DQB1, DPB1) for transplantation matching and disease association studies.

CYP2C19 poor metabolizer

Reduced activation of clopidogrel; alternative antiplatelet therapy (prasugrel, ticagrelor) recommended after PCI.

UGT1A1*28

Polymorphism causing reduced glucuronidation of irinotecan metabolite SN-38; increases risk of neutropenia and diarrhea.

NGS coverage depth

Number of times a nucleotide is sequenced; ≥30x for germline variant detection, ≥500x for somatic variant detection.

FASTQ format

Text file storing raw sequence reads and per-base quality scores (Phred); standard output from next-generation sequencers.