Human Genetics: DNA Structure, Replication, Gene Expression, and Sex Determination

Comprehensive vocabulary flashcards covering the molecular genetics of DNA structure, replication, sex determination, transcription, translation, protein folding, epigenetics, and gene regulation based on Chapters 6, 9, 10, and 11 of Ricki Lewis's Human Genetics.

Nuclein

The original name given by Friedrich Miescher in 1871 to the acidic, phosphorus- and nitrogen-rich material isolated from the nuclei of white blood cells in pus; later termed nucleic acid.

Inborn Errors of Metabolism

Inherited conditions linked by Archibald Garrod in 1902 to deficiencies in specific cellular enzymes, as demonstrated in his study of alkaptonuria.

Transformation

The mechanism discovered by Frederick Griffith in 1928 by which bacteria take up foreign genetic material from their environment and incorporate it into their genome, acquiring new heritable traits.

Transforming Principle

The chemical substance identified by Avery, MacLeod, and McCarty in 1944 as DNA, demonstrated when treatment with DNase destroyed the ability of heat-killed type S bacteria to transform type R bacteria.

Hershey-Chase Experiment

The 1953 blender experiment using $^{35}\text{S}$-labeled viral protein coats and $^{32}\text{P}$-labeled viral DNA in bacteriophages infecting E. coli, proving that viral DNA, not protein, enters bacteria to direct viral replication.

Nucleotide

The fundamental building block of nucleic acids, consisting of a 5-carbon pentose sugar (ribose or deoxyribose), a phosphate group attached at the $5'$ position, and a nitrogenous base attached at the $1'$ position.

Purines

Large, double-ring nitrogenous bases found in DNA and RNA, specifically adenine (A) and guanine (G).

Pyrimidines

Single-ring nitrogenous bases found in nucleic acids, consisting of cytosine (C) and thymine (T) in DNA, and cytosine (C) and uracil (U) in RNA.

Chargaff's Rules

The principle established by Erwin Chargaff stating that in double-stranded DNA, the total amount of purines equals the total amount of pyrimidines ($\text{A} + \text{G} = \text{T} + \text{C}$), meaning $\text{A} = \text{T}$ and $\text{G} = \text{C}$.

Photo 51

The historic X-ray diffraction image of B-form DNA captured by Rosalind Franklin after 100 hours of exposure, revealing the characteristic X pattern indicating a helical structure with symmetrical subunits.

Phosphodiester Bond

The covalent chemical bond linking the $3'$ hydroxyl group of one deoxyribose sugar to the $5'$ phosphate group of the adjacent nucleotide in a polynucleotide chain.

Antiparallel

The head-to-toe spatial orientation of the two complementary polynucleotide strands in a DNA double helix, where one strand runs $5'$ to $3'$ and the opposing strand runs $3'$ to $5'$.

Nucleosome

A bead-like structural unit of chromatin measuring $10\,\text{nm}$ in diameter, composed of DNA wrapped around an octamer core of eight histone proteins (two each of H2A, H2B, H3, and H4).

CTCF Anchor Protein

A specialized protein that anchors DNA loops at approximately 10,000 genomic locations, facilitating higher-order chromatin organization into loop domains.

Semiconservative Replication

The mechanism of DNA duplication proven by Meselson and Stahl, wherein each replicated double helix consists of one intact original parental strand and one newly synthesized daughter strand.

Replication Fork

The Y-shaped active site along a double-stranded DNA molecule where the parental strands unwound by helicase separate and new complementary strands are synthesized.

Helicase

The enzyme that initiates DNA strand separation at the origin of replication by breaking hydrogen bonds holding complementary base pairs together.

Single-Strand Binding Proteins

Proteins that stabilize separated single parental DNA strands during replication to prevent them from re-annealing to each other.

Primase

An RNA polymerase enzyme that synthesizes a short RNA primer complementary to the template DNA strand to provide a free $3'$ hydroxyl group for DNA polymerase.

DNA Polymerase

The enzyme that synthesizes new DNA strands exclusively in the $5'$ to $3'$ direction by binding complementary deoxynucleotides to a template and providing proofreading activity to remove errors.

DNA Ligase

The enzyme that catalyzes the formation of phosphodiester bonds to join Okazaki fragments and seal nicks in the sugar-phosphate backbone.

Okazaki Fragments

Short, discontinuous segments of newly synthesized DNA formed along the $5'$ to $3'$ lagging strand template during DNA replication.

Polymerase Chain Reaction (PCR)

An in vitro technique using a heat-stable polymerase to exponentially amplify a target DNA sequence through repeated cycles of denaturation, primer annealing, and extension, yielding over 10 billion copies after 30 cycles.

Taq Polymerase

A heat-resistant DNA polymerase utilized in PCR that binds to the $3'$ ends of annealed primers to add complementary deoxynucleotides during the elongation phase.

Sanger Sequencing

A DNA sequencing method that deduces nucleotide order by using chain-terminating dideoxynucleotides (ddNTPs) that halt synthesis at specific bases, followed by electrophoretic fragment separation.

Dideoxynucleotide Triphosphate (ddNTP)

A modified nucleotide lacking hydroxyl groups at both the $2'$ and $3'$ carbon positions of the sugar ring, which terminates DNA strand elongation when incorporated.

Next-Generation Sequencing

A massively parallel sequencing technology that immobilizes millions of DNA fragments on solid substrates to read their sequences simultaneously, reducing the time required to sequence a human genome from 10 years to mere hours.

Heterogametic Sex

The biological sex producing gametes that carry differing sex chromosomes (such as XY human males, XO male grasshoppers, or ZW female birds and snakes).

Homogametic Sex

The biological sex producing gametes that all carry the same sex chromosome (such as XX human females, XX female grasshoppers, or ZZ male birds and snakes).

Wolffian Ducts

Embryonic reproductive duct structures present during the fifth week of human prenatal development that differentiate into internal male reproductive structures under the influence of testosterone.

Müllerian Ducts

Embryonic duct structures present during early bipotential development that develop into the female reproductive tract (uterine tubes, uterus, and upper vagina) in the absence of SRY gene activity.

SRY Gene

A master switch gene on the short arm of the Y chromosome that encodes a transcription factor directing undifferentiated gonads to develop into testes and destroying female precursor structures.

Wnt4 Gene

A critical gene required for the proper development and maturation of female reproductive structures; mutations lead to elevated male sex hormones and failure of the ovaries, uterus, and vagina to develop.

Pseudoautosomal Regions (PAR1 and PAR2)

Homologous regions located at both tips of the Y chromosome comprising roughly $5\%$ of its length and containing 63 genes shared with the X chromosome that can cross over with it.

Male-Specific Region of the Y (MSY)

The non-recombining portion of the human Y chromosome that contains male-specific genes, palindromic sequences, and fertility-determining factors such as the SRY gene and AZF.

Pseudohermaphroditism

A condition in which an individual exhibits both male and female anatomical sexual structures at different stages of life, or possesses external genitalia discordant with chromosomal and gonadal sex.

Androgen Insensitivity Syndrome

An X-linked condition in which a genetic male ($\text{XY}$) possesses normal testosterone production but lacks functional androgen receptors, leading to external female anatomical development.

5-Alpha Reductase Deficiency

An inborn condition where an enzyme defect prevents the conversion of testosterone to dihydrotestosterone (DHT), resulting in internal male anatomy paired with female-appearing external genitalia until puberty.

Congenital Adrenal Hyperplasia

An inherited enzyme block in steroid metabolism causing excess adrenal androgen accumulation, leading to precocious puberty in males or virilization of external genitalia in females.

Sex Ratio

The proportion of males to females in a population, calculated as (\text{# of males} / \text{# of females}) \times 1000, evaluated as primary (at conception), secondary (at birth), or tertiary (at maturity).

Hemizygous

The genetic state of having only a single copy of a gene or chromosome in an otherwise diploid organism, such as human males having only one copy of X-linked loci.

Ichthyosis

An X-linked recessive disorder characterized by rough, scaly skin caused by an inherited enzyme deficiency that halts the normal removal of cholesterol from epidermal cells.

Sex-Limited Trait

A trait or condition encoded by an autosomal or X-linked gene that is expressed exclusively in one sex due to anatomical or physiological limitations, such as beard growth, milk production, or preeclampsia.

Sex-Influenced Trait

A trait where the expression of an allele is dominant in one sex but recessive in the other due to hormonal environment differences, such as male pattern baldness.

X Inactivation

The epigenetic dosage-compensation process in mammalian female cells controlled by the XIST gene, in which one of the two X chromosomes is permanently silenced through methylation early in embryonic development.

Barr Body

A condensed, dark-staining structure visible in the interphase nucleus of female somatic cells, representing the transcriptionally inactive, methylated X chromosome.

Manifesting Heterozygote

A heterozygous female who expresses the phenotype of an X-linked recessive disorder because unfavorable random X inactivation silenced the normal allele in a significant proportion of relevant tissues.

Calico Cat (X-Inactivation Mosaicism)

A distinct phenotype seen almost exclusively in female cats that are heterozygous for an X-linked coat color gene, exhibiting patches of orange and black fur determined by which X chromosome was randomly inactivated.

Genomic Imprinting

An epigenetic modification where methyl groups bind to specific genes during gametogenesis based on parental sex, repressing gene expression from either the maternal or paternal allele in the offspring.

Prader-Willi Syndrome

A neurodevelopmental disorder resulting from the inheritance of a small deletion on chromosome 15 that originated from the father, or maternal uniparental disomy of chromosome 15.

Angelman Syndrome

A neurogenetic disorder resulting from the inheritance of a deletion on chromosome 15 that originated from the mother, leaving the maternally active genes missing.

Central Dogma

The directional conceptual framework of molecular biology stating that genetic information flows sequentially from DNA to RNA via transcription, and from RNA to protein via translation.

Template Strand

The specific DNA strand oriented $3'$ to $5'$ that RNA polymerase reads to synthesize a complementary single-stranded RNA transcript.

Coding Strand

The non-template DNA strand running $5'$ to $3'$ that possesses the identical sequence to the transcribed RNA molecule, with thymine present instead of uracil.

Messenger RNA (mRNA)

The linear class of RNA ranging from 500 to 4,500 bases in length that carries transcribed protein-encoding instructions organized into triplet codons from the nucleus to ribosomes.

Codon

A consecutive sequence of three mRNA nucleotides that specifies a particular amino acid or serves as a translational start or stop signal.

Transfer RNA (tRNA)

A small adaptor RNA molecule 75 to 80 nucleotides long with a 2D cloverleaf and 3D inverted-L shape, containing an anticodon loop at one end and an amino acid-accepting stem ending in $3'\text{-ACC}$ at the other.

Ribosomal RNA (rRNA)

Structural and catalytic RNA components ranging from 100 to 3,000 nucleotides long that associate with ribosomal proteins to assemble ribosomal subunits and catalyze peptide bond formation as ribozymes.

Transcription Factors

Proteins that recognize and bind specific promoter sequences on DNA, forming a pre-initiation apparatus that recruits RNA polymerase to start transcription.

TATA Box

A conserved, thymine- and adenine-rich DNA sequence located within gene promoters that binds TATA-binding protein to position the transcription apparatus.

Exons

The expressed sequences of pre-mRNA that are retained and spliced together during RNA processing to form the mature mRNA translated into protein.

Introns

Intervening non-coding RNA sequences in pre-mRNA that outnumber and outsize exons and are excised by small nuclear ribonucleoproteins (snRNPs) within the spliceosome.

Alternative Splicing

A cellular mechanism occurring in approximately $95\%$ of human genes in which exons are recombined or omitted in various arrangements to produce distinct protein isoforms from a single pre-mRNA.

Synonymous Codons

Different three-base mRNA triplet sequences that specify and code for the identical amino acid, reflecting the degenerate nature of the genetic code.

Nonsynonymous Codons

Codons that differ in nucleotide sequence and code for entirely different amino acids.

Reading Frame

The specific non-overlapping triplet grouping in which mRNA bases are translated into an amino acid sequence, established by the start codon (AUG).

A Site

The aminoacyl binding site on the ribosome where incoming aminoacyl-tRNA complexes bearing their respective amino acids enter during translational elongation.

P Site

The peptidyl site of the ribosome that holds the tRNA carrying the growing polypeptide chain and accommodates the initiator methionyl-tRNA during translation initiation.

E Site

The exit site of the ribosome where deacylated tRNAs are briefly held before detaching and releasing into the cytoplasm.

Chaperone Proteins

Specialized helper proteins that bind to nascent, growing polypeptide chains emerging from ribosomes to stabilize folding intermediates and prevent misfolding or improper aggregation.

Ubiquitin

A small regulatory polypeptide attached in multi-unit chains to misfolded, damaged, or unneeded proteins to target them for degradation by proteasomes.

Proteasome

A multi-protein, barrel-shaped cellular complex that straightens and degrades ubiquitin-tagged proteins into short peptides and recyclable amino acids.

Prions

Infectious, protein-only pathogens lacking nucleic acids that cause fatal neurodegenerative diseases by inducing normal alpha-helical prion proteins to adopt an abnormal, beta-pleated sheet conformation.

Kuru

The first recognized human prion disease, discovered among the Fore people of Papua New Guinea, which spread through the ritualistic cannibalistic consumption of deceased kin.

Transcriptome

The complete collection of messenger RNA transcripts synthesized by a specific cell, tissue, or organism under defined environmental conditions or developmental stages.

Housekeeping Genes

Genes that are continually expressed across all cell types to maintain essential, baseline cellular functions and survival.

Globin Chain Switching

The developmental regulation of hemoglobin subunit production replacing embryonic globin chains ($2\epsilon + 2\zeta$) with fetal chains ($2\gamma + 2\alpha$), and finally adult chains ($2\beta + 2\alpha$) by four years of age.

Diseasome

A comprehensive network map connecting distinct human clinical disorders that share altered gene expression patterns, such as the association identified between Duchenne muscular dystrophy and heart disease.

Chromatin Remodeling

The reversible modification of histone proteins through the addition of acetyl, phosphate, or methyl groups that shifts nucleosome packing to regulate gene transcription.

Histone Acetylation

The enzymatic addition of acetyl groups ($\text{CH}_3\text{CO}_2$) to positively charged histone tails, neutralizing their charge and relaxing their hold on DNA to expose promoter TATA boxes for transcription.

MicroRNAs (miRNAs)

Short, noncoding RNA molecules 21 to 22 nucleotides in length that act as post-transcriptional dimmer switches by binding complementary mRNA sequences to block translation or trigger mRNA degradation.

Microproteins

Polypeptides containing fewer than 100 amino acids that fit into regulatory cavities of larger proteins, such as ion channels and cell receptors, to alter their activity.

Circular RNAs (circRNAs)

Covalently closed loop RNA molecules formed via non-canonical alternative splicing that are resistant to exonucleolytic degradation and function as microRNA sponges.

Dentinogenesis Imperfecta

A genetic disorder affecting tooth development caused by abnormal processing of the dentin sialophosphoprotein (DSPP) precursor protein, which normally cleaves into DPP (dentin phosphoprotein) and DSP (dentin sialoprotein).