Molecular Genetics, Cytogenetics, and Inherited Disorders

Comprehensive vocabulary flashcards covering DNA damage and repair mechanisms, recombinant DNA technologies, molecular cloning, sequencing platforms, genetic mapping, cytogenetics, and autosomal recessive diseases including albinism and cystic fibrosis.

Tautomers

Alternative chemical conformations of purines and pyrimidines that differ only in the position of a proton, causing anomalous base-pairing arrangements during DNA replication that can lead to transition mutations.

Base Excision Repair (BER)

A high-fidelity DNA repair pathway for single-strand lesions where a DNA glycosylase recognizes and excises an incorrect base (such as uracil), an AP endonuclease nicks the damaged strand, and DNA polymerase and DNA ligase fill the gap.

Nucleotide Excision Repair (NER)

A high-fidelity repair pathway in which uvr gene products and nucleases excise bulky DNA lesions, such as cyclobutane pyrimidine dimers (CPD) and (6-4)PP adducts caused by UV light, before DNA polymerase I and ligase rebuild the strand.

Non-Homologous End Joining (NHEJ)

A low-fidelity, error-prone repair process for double-strand DNA breaks that directly religates free blunt DNA ends without a homologous template, frequently introducing deletions, insertions, or translocations.

Xeroderma Pigmentosum

A hereditary disorder caused by mutations in nucleotide excision repair enzymes, leading to extreme cellular sensitivity to UV radiation and a $1000$-fold increased risk of skin cancers.

Dominant Negative Effect

A mutation effect wherein an inactive mutant monomer prevents the proper assembly or function of a multimeric protein complex formed with wild-type monomers, as observed in p53 tetramers promoting cancer development.

Restriction Enzymes

Sequence-specific bacterial endonucleases that recognize and cleave foreign viral DNA, commonly cutting within symmetrical palindromic recognition sequences to generate sticky or blunt ends.

Yeast Two-Hybrid System

A molecular screening system exploiting the separable DNA-binding domain (DBD) and activation domain (AD) of GAL4 to identify protein-protein interactions by expressing them as 'bait' and 'prey' fusions that activate reporter genes like HIS3.

Taq Polymerase

A heat-stable DNA polymerase isolated from Thermophilus aquaticus that withstands high PCR denaturation temperatures ($92\text{--}95\,^\circ\text{C}$), eliminating the need to replenish enzyme after each thermal cycle.

RNA Interference (RNAi)

A biological mechanism utilized to silence target gene expression wherein synthetic double-stranded siRNAs incorporate into the RNA-induced silencing complex (RISC) to bind and direct the degradation of complementary mRNA molecules.

Single Guide RNA (sgRNA)

An engineered synthetic RNA molecule combining crRNA and tracrRNA sequences that directs Cas9 nuclease to generate a site-specific double-strand break adjacent to a protospacer adjacent motif (PAM) in target genomic DNA.

Fluorescence In Situ Hybridisation (FISH)

A cytogenetic technique in which fluorescently labeled denatured DNA fragments hybridize directly to intact metaphase chromosomes mounted on a microscope slide to determine the physical location of specific gene sequences.

Spectral Karyotyping (SKY)

A cytogenetic imaging approach that labels chromosome-specific DNA probes with distinct combinations of fluorophores to paint each pair of chromosomes in a distinct color, facilitating detection of translocations and structural rearrangements.

Southern Blotting

A technique for identifying specific DNA fragments from complex restriction-digested mixtures by transferring electrophoretically separated fragments to a membrane and probing them with a complementary labeled single-stranded DNA sequence.

Variable Number Tandem Repeats (VNTRs)

Hypervariable repetitive genomic DNA sequences of $15\text{--}100\,\text{bp}$ repeated in tandem up to hundreds of times, analyzed via flanking restriction digestion and Southern blotting to generate distinctive DNA fingerprints.

Dideoxynucleotide (ddNTP)

A modified nucleotide lacking hydroxyl groups ($-\text{OH}$) at both the $2'$ and $3'$ positions of the ribose ring, which blocks subsequent phosphodiester bond formation and terminates DNA chain elongation in Sanger sequencing.

Nanopore Sequencing

A third-generation sequencing platform that translates characteristic fluctuations in electrical current into nucleotide sequences as single DNA strands pass through protein pores embedded in a synthetic membrane.

Short Tandem Repeats (STRs)

Abundant polymorphic microsatellite loci containing simple repeat motifs of $2$, $3$, or $4\,\text{bp}$ whose varying repeat numbers generate allele size differences resolvable by PCR with fluorescently labeled primers.

Single Nucleotide Polymorphisms (SNPs)

Variations occurring at single base positions across genomes that usually feature two common alleles, frequently evaluated on microarray chips for high-density genotyping and disease mapping.

Whole Exome Sequencing (WES)

A targeted next-generation sequencing method focusing selectively on protein-coding exons and approximately $20\,\text{bp}$ of adjacent intronic boundaries to identify mutations responsible for monogenic genetic disorders.

Genome-Wide Association Studies (GWAS)

An observational genetic approach comparing hundreds of thousands to millions of common SNP markers between large cohorts of affected individuals and controls to identify variants contributing small effect sizes to complex polygenic traits.

Aneuploidy

A chromosomal condition characterized by an atypical chromosome number deviating from the normal diploid count by the gain or loss of specific individual chromosomes, predominantly caused by meiotic nondisjunction.

Turner Syndrome

A female sex-chromosome monosomy ($45,\text{X}$) occurring in approximately $1:2000$ live female births, presenting with short stature, malformed ovaries, and cardiovascular defects caused by haploinsufficiency of pseudoautosomal genes.

Polyploidy

The condition of possessing three or more complete haploid chromosome sets ($3n$, $4n$, etc.), which causes sterility in triploid plants (such as commercial seedless watermelons and bananas) due to meiotic chromosome segregation failure.

Endopolyploidy

The presence of multiple complete sets of chromosomes within specific differentiated cell types of an otherwise diploid organism, notably occurring in insect salivary glands and mammalian liver cells.

Cri du Chat Syndrome

A rare genetic condition caused by a sporadic partial deletion of the terminal short arm of chromosome $5$ ($5\text{p}$), clinically defined by developmental delay, microcephaly, and a distinctive cat-like infant cry.

Reciprocal Translocation

A chromosomal rearrangement resulting from double-strand breaks in two non-homologous chromosomes with reciprocal swapping of the acentric fragments, often resulting in unbalanced, deficient gametes during meiotic segregation.

Autosomal Recessive Inheritance

A mode of inheritance wherein an affected individual inherits two mutant alleles from asymptomatic carrier parents, presenting an equal sex distribution, a $25\%$ recurrence risk per birth, and elevated prevalence among consanguineous pairings.

Oculocutaneous Albinism Type 1A (OCA1A)

A severe autosomal recessive disorder resulting from biallelic null mutations in the TYR gene, completely eliminating tyrosinase enzyme activity and leading to total absence of melanin, white hair, nystagmus, photophobia, and lack of binocular depth perception.

Oculocutaneous Albinism Type 1B (OCA1B)

A milder form of albinism caused by loss-of-function TYR mutations that significantly decrease, but do not fully abolish, tyrosinase activity or stability, permitting residual pigment formation resulting in fair or yellow-tinted hair.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

An ATP-regulated epithelial cell membrane chloride ion channel whose dysfunction causes mucus accumulation in the lungs, pancreatic insufficiency, male infertility, and elevated chloride levels in sweat.

$$\text{F508del}$$

The most common cystic fibrosis-causing mutation, characterized by a three-base-pair deletion in CFTR resulting in a misfolded protein that is prematurely degraded and acts predominantly as a null allele.

$$\text{G551D}$$

The third most common CFTR mutation, caused by a missense substitution that yields a correctly localized membrane channel with severely impaired channel gating and gating opening capacity.

CFTR Potentiator

A class of targeted small-molecule therapeutics (e.g., Ivacaftor) that binds to cell-surface localized mutant CFTR channels like $\text{G551D}$ to increase the open probability of the channel and facilitate chloride ion conductance.

CFTR Corrector

A pharmacological class of chaperone drugs (such as Lumacaftor, Tezacaftor, and Elexacaftor) designed to promote the proper tertiary folding and membrane trafficking of misfolded CFTR proteins bearing processing defects such as $\text{F508del}$.