Human Genome, Gene Regulation, and Genetic Basis of Disease

Vocabulary flashcards covering the human genome structure, transcription factors, types of mutations, pharmacogenomic variations, and modes of inheritance for single-gene and polygenic disorders.

Exons

The coding regions of a gene that encode proteins, ribosomal RNAs, microRNAs, tRNAs, and other functional RNAs, making up approximately $2\%$ of the human genome.

Introns

Non-coding intervening sequences located within a gene that account for approximately $5\%$ of the human genome.

RNA Polymerase I

The nuclear RNA polymerase enzyme responsible for transcribing ribosomal RNA-coding genes.

RNA Polymerase II

The nuclear RNA polymerase enzyme that transcribes genes coding for proteins, microRNAs (miRNAs), and small nucleolar RNAs.

RNA Polymerase III

The nuclear RNA polymerase enzyme that transcribes transfer RNA (tRNA)-coding genes.

Basal Transcription Apparatus

The multi-protein transcription complex composed of RNA polymerase II and general transcription factors comprising $27$ total proteins.

TFIID

A general transcription factor with $12$ subunits ($1\text{ TBP}$ and $11\text{ TAFs}$) that recognizes the TATA box and other DNA sequences near the transcription start point.

TFIIB

A general transcription factor composed of $1$ subunit that recognizes the BRE element in promoters and accurately positions RNA polymerase at the start site.

TFIIF

A general transcription factor composed of $3$ subunits that stabilizes RNA polymerase interactions with TBP and TFIIB, helping attract TFIIE and TFIIH.

TFIIE

A general transcription factor consisting of $2$ subunits that attracts and regulates TFIIH.

TFIIH

A general transcription factor with $9$ subunits that unwinds DNA at the transcription start point, phosphorylates C-terminal Ser residues of RNA polymerase, and releases RNA polymerase from the promoter.

Synonymous Mutation

A point mutation (also termed a silent mutation) where a single nucleotide substitution does not alter the resulting amino acid sequence.

Nonsense Mutation

A point mutation where a single nucleotide change converts an amino acid-specifying codon into a premature STOP codon.

Missense Mutation

A non-synonymous point mutation where a single nucleotide substitution causes a codon to specify a different amino acid.

frame shift mutation

A genetic mutation caused by the insertion or deletion of a number of nucleotides not divisible by three, shifting the mRNA reading frame.

Single Nucleotide Polymorphism (SNP)

A single base pair alteration in the DNA sequence occurring with a frequency of about $1\text{ SNP}$ per $1,000\text{ base pairs}$, totaling more than $3\text{ million}$ per human genome.

De Novo Mutation

A genetic alteration present for the first time in a family member that was not directly inherited from either parent.

Homozygous

Having two identical alleles or sequence copies at a specific locus on homologous chromosomes.

Heterozygous

Having two different alleles or sequence copies at a specific locus on homologous chromosomes.

Wild-type Allele

The common, functional gene version or reference allele standard in a population.

CYP2D6

A cytochrome P450 enzyme displaying marked genetic polymorphism that metabolizes codeine into morphine.

Genotype

The specific genetic makeup or unique set of genes possessed by an individual organism.

Phenotype

The observable physical, physiological, or behavioral traits of an organism resulting from its genotype interacting with the environment.

Monogenic Disorder

A disorder caused by a mutation in a single gene that carries a large phenotypic effect, such as Cystic Fibrosis or Sickle Cell Disease.

Polygenic Disorder

A multifactorial disease caused by combined variations across two or more genes interacting with environmental factors, where each gene effect is small.

Mosaic Mutation

A subtype of de novo mutation occurring during post-zygotic mitotic divisions, resulting in two or more genetically distinct cell populations in one individual.

Somatic Mutation

A non-inherited, spontaneous mutation occurring in non-germline body cells, frequently caused by replication errors or environmental insults.

Germline Mutation

A mutation occurring in reproductive sperm or egg cells that can be transmitted to offspring and expressed in every cell of their body.

Dominant Allele

An allele that is phenotypically expressed even when paired with a contrasting recessive allele in a heterozygous individual.

Recessive Allele

An allele whose phenotypic effect is observable only when paired with another identical recessive allele in a homozygous individual.

CFTR Gene

The gene on chromosome $7$ that encodes the cystic fibrosis transmembrane conductance regulator chloride channel, mutated in Cystic Fibrosis.

Trikafta

A triple-combination CFTR modulator drug that stabilizes the $\Delta F508\text{-CFTR}$ protein to aid correct folding, cellular trafficking, and channel gating.

Hemophilia

An X-linked recessive bleeding disorder characterized by impaired blood coagulation due to deficiency in factor VIII (Hemophilia A) or factor IX (Hemophilia B).

Sickle Cell Anemia

An autosomal recessive blood disease caused by a point mutation in the hemoglobin gene that substitutes Glutamic acid with Valine ($\text{GAG} \rightarrow \text{GUG}$).

Duchenne Muscular Dystrophy (DMD)

A severe X-linked recessive muscle disease caused by mutations in the dystrophin gene (the largest human gene with $79$ exons) that prevent dystrophin expression.

Eteplirsen

An FDA-approved drug designed to induce exon $51$ skipping during pre-mRNA splicing to restore an in-frame mRNA transcript in DMD patients.

Huntington's Disease

An autosomal dominant neurodegenerative disorder caused by an expansion of CAG trinucleotide repeats ($>35\text{ repeats}$) in the huntingtin gene on chromosome $4$.

Familial Hypercholesterolemia (FH)

An autosomal dominant disorder of cholesterol metabolism caused by variants in the LDLR gene on chromosome $19$, producing high circulating LDL levels.

BRCA1 and BRCA2

Tumor suppressor genes involved in double-strand DNA repair whose pathogenic mutations significantly increase inherited risks for breast and ovarian cancers.