Cytogenetics: Cell Cycle, Heredity, and Molecular Techniques

Comprehensive vocabulary flashcards covering the cell cycle, mitosis, meiosis, Mendelian heredity, mutations, cytogenetic laboratory methods, and chromosomal disorders.

Cell Cycle

The orderly sequence of events in which a cell duplicates its contents and divides into two, serving as the essential mechanism by which all living things reproduce.

Cyclin-Dependent Protein Kinases (Cdks)

The major protein kinases of the cell cycle control system that are present in all phases and are cyclically activated by binding to cyclin partners to phosphorylate target proteins.

Anaphase-Promoting Complex or Cyclosome (APC/C)

A regulatory complex that tags $M$ and $S$ cyclins for destruction in proteasomes via ubiquitylation, inactivating cyclin-Cdk complexes to drive exit from mitosis.

Wee1

An inhibitory kinase that places inhibitory phosphates onto cyclin-Cdk complexes to keep them inactive prior to phase transition.

Cdc25

An activating phosphatase that removes inhibitory phosphates from cyclin-Cdk complexes to trigger their enzymatic activation and drive cell cycle progression.

p27

A Cdk inhibitor protein (CKI) that binds directly to active cyclin-Cdk complexes to block their assembly or activity.

Retinoblastoma (Rb) Protein

A nuclear protein that binds and represses transcription regulators of cell proliferation; it is inactivated by phosphorylation via $G_1\text{-Cdk}$ and $G_1/S\text{-Cdk}$ in response to mitogens.

p53

A tumor suppressor protein that accumulates and becomes phosphorylated upon DNA damage, stimulating transcription of the Cdk inhibitor $p21$ or inducing apoptosis if damage is severe.

p21

A Cdk inhibitor protein induced by $p53$ that binds and inactivates $G_1/S\text{-Cdk}$ and $S\text{-Cdk}$, preventing progression into $S$ phase until DNA damage is repaired.

Prereplicative Complex (preRC)

A multi-protein complex assembled at replication origins during $G_1$ consisting of the Origin Recognition Complex (ORC), Cdc6, and loaded DNA helicase.

Cohesin

A protein complex that encircles duplicated sister chromatids along their length to keep them tied together until anaphase.

Separase

The protease that cleaves cohesin linkages during anaphase, enabling sister chromatids to separate and move toward opposite spindle poles.

Mitotic Spindle

A bipolar cytoskeletal apparatus composed of microtubules and motor proteins that segregates duplicated chromosomes equally between daughter cells during mitosis.

Contractile Ring

A dynamic cytoskeletal structure assembled beneath the plasma membrane from actin and myosin filaments that constricts to pinch an animal cell into two daughter cells during cytokinesis.

Bi-orientation

The stable attachment of sister chromatids to kinetochore microtubules emanating from opposite spindle poles during prometaphase.

Metaphase Plate

The imaginary plane midway between the two spindle poles where kinetochores and duplicated chromosomes align during metaphase.

Cleavage Furrow

An indentation that appears at the cell equator during anaphase as the initial visible sign that the cell has commenced cytokinesis.

Bivalent

A four-chromatid structure formed during meiotic prophase I when duplicated homologous maternal and paternal chromosomes pair up along their length.

Chiasma

An $X$-shaped physical connection between non-sister chromatids of homologous chromosomes representing the cytological site of a crossing-over event.

Synaptonemal Complex

A zipper-like protein structure that holds paired homologous chromosomes in precise alignment during meiotic prophase I to facilitate crossing-over.

Allele

An alternative version of a gene that occupies a specific locus on homologous chromosomes and may have slight nucleotide differences.

Law of Segregation

Mendel's first law stating that the two alleles for each inherited trait separate during gamete formation and unite at random at fertilization.

Law of Independent Assortment

Mendel's law stating that alleles of different genes assort independently during gamete formation, typically yielding a $9:3:3:1$ phenotypic ratio in dihybrid crosses.

Co-inheritance

The joint transmission of genes located in close proximity on the same chromosome due to inadequate space between them for crossing-over to occur.

Gain-of-Function Mutation

A mutation that enhances or increases the normal activity of a gene product, usually conferring a dominant phenotypic effect.

Loss-of-Function Mutation

A mutation that reduces or completely abolishes the functional activity of a gene product, typically exhibiting a recessive mode of inheritance.

Missense Mutation

A point mutation in which a single base substitution alters a codon to specify a different amino acid in the encoded polypeptide.

Nonsense Mutation

A point mutation in which a nucleotide change converts an amino acid-specifying codon into a premature stop codon, terminating translation.

Frameshift Mutation

A mutation resulting from the insertion or deletion of a number of nucleotides that is not a multiple of three, altering the downstream triplet reading frame.

Pseudogene

A nonfunctional, defective copy of a gene that shares sequence similarity with a functional gene family member but has accumulated mutations that prevent its expression.

Exon Shuffling

A molecular evolutionary mechanism where protein-coding exons of different genes are recombined within intervening intron sequences to create novel combinations.

Mobile Genetic Elements

DNA sequences (transposons) capable of moving from one chromosomal site to another, making up approximately $50\%$ of the human genome.

Single-Nucleotide Polymorphisms (SNPs)

Single base-pair differences that occur at a frequency of at least $1\%$ within a population, appearing roughly once every $1000$ nucleotide pairs in human DNA.

Dideoxyribonucleoside Triphosphate (ddNTP)

A synthetic nucleotide that lacks a $3'\text{-OH}$ group on the ribose ring, terminating DNA strand elongation during Sanger sequencing.

In Situ Hybridization

A cytogenetic procedure utilizing labeled DNA or RNA probes with fluorescent dyes or radioactive tags to locate specific nucleotide sequences directly inside intact cells or tissues.

CRISPR-Cas9

A targeted genome-editing method employing a guide RNA and the bacterial Cas9 endonuclease to produce double-strand breaks at specific genomic sites, inducing targeted gene knockouts.

Karyotyping

The cytogenetic preparation and visual arrangement of metaphase chromosomes ordered by size and shape to detect numerical and structural aberrations.

Chromosomal Deletion

A structural chromosomal aberration occurring when a fragment of a chromosome is lost, leaving the affected chromosome deficient of specific genes.

Chromosomal Inversion

A structural chromosomal mutation in which a broken segment reattaches to the original chromosome in reverse orientation.

Chromosomal Translocation

A structural rearrangement involving the transfer of a chromosomal segment to a non-homologous chromosome, occurring most commonly as an exchange between two chromosomes.

Nondisjunction

The failure of homologous chromosome pairs to separate properly during meiosis I, or sister chromatids during meiosis II, causing gametes with abnormal chromosome numbers.

Aneuploidy

The condition of having an abnormal chromosome count that differs from the normal diploid number by one or more individual chromosomes.

Cri du Chat Syndrome

A human congenital condition caused by a deletion on the short arm of chromosome 5 ($5\text{p-}$, characterized by microcephaly, intellectual disability, and a high-pitched cat-like cry.

Philadelphia Chromosome

A shortened derivative chromosome 22 created by reciprocal translocation between chromosomes 9 and 22, strongly associated with chronic myelogenous leukemia (CML).

Prader-Willi Syndrome

A genetic condition caused by a deletion on the long arm of chromosome 15 ($15\text{q-}$, leading to poor feeding and hypotonia in infancy followed by hyperphagia and severe obesity.

Down Syndrome

An autosomal aneuploidy syndrome caused by Trisomy 21 ($47$ total chromosomes), associated with developmental delay, epicanthal folds, and broad short skull features.

Patau's Syndrome

An autosomal disorder caused by Trisomy 13 ($47$ chromosomes), characterized by microcephaly, holoprosencephaly/facial clefting, polydactyly, and severe developmental failure.

Edward's Syndrome

An autosomal trisomy condition involving chromosome 18 ($47$ chromosomes), characterized by open skull sutures, flexion deformities of the fingers, and mortality typically within $4\text{ months}$.

Turner Syndrome

A female sex chromosome monosomy ($45\text{, XO}$) resulting from nondisjunction, characterized by short stature, low hairline, rudimentary gonadal streak ovaries, and primary amenorrhea.

Klinefelter Syndrome

A male sex chromosome trisomy ($47\text{, XXY}$) resulting from nondisjunction, presenting with small testes, sterility, and variable gynecomastia.

Cell cycle

The essential mechanism by which all living organisms reproduce, consisting of an orderly sequence of events in which a cell duplicates its contents and divides into two.

Early fly embryo cell cycle duration

A cell cycle lasting $8\text{ minutes}$.

Early frog embryo cell cycle duration

A cell cycle lasting $30\text{ minutes}$.

Mammalian intestinal epithelial cell cycle duration

A cell cycle lasting approximately $\sim 12\text{ hours}$.

Mammalian fibroblasts in culture cell cycle duration

A cell cycle lasting approximately $\sim 20\text{ hours}$.

Terminally differentiated cells

Specialized cells such as neurons and muscle cells that no longer divide, have dismantled their cell-cycle control system, and have permanently turned off their cyclin and Cdk genes.

Interphase

The prolonged phase of the cell cycle during which the cell transcribes genes, synthesizes proteins, enlarges in mass, duplicates cytoplasmic organelles, and replicates its nuclear DNA.

G1 phase

The gap phase occurring between the M phase and the S phase where the cell grows and gathers nutrients to prepare for DNA synthesis.

S phase

The synthesis phase of the cell cycle in which cellular DNA replication occurs.

G2 phase

The gap phase occurring between the S phase and the M phase during which the cell checks that DNA replication is complete and undamaged before entering mitosis.

Checkpoints

Critical transition points in the cell cycle where the control system pauses progression to verify that required processes have completed without abnormality before advancing.

Cyclin-dependent protein kinases (Cdks)

Core regulatory protein kinases present throughout all phases of the cell cycle that are switched on in a cyclical pattern upon binding to activating cyclins.

G1-Cdk

A cyclin-Cdk complex consisting of Cyclin D and Cdk4 or Cdk6 that drives cell progression through the G1 phase.

G1/S-Cdk

A cyclin-Cdk complex composed of Cyclin E and Cdk2 that helps launch the S phase.

S-Cdk

A cyclin-Cdk complex composed of Cyclin A and Cdk2 that initiates DNA replication and prevents re-replication by phosphorylating replication origin components.

M-Cdk

A cyclin-Cdk complex consisting of Cyclin B and Cdk1 that drives entry into and progression through mitosis.

Anaphase-promoting complex or cyclosome (APC/C)

A protein complex that marks M and S cyclins for proteasomal degradation via ubiquitylation, inactivating the Cdk complex and concluding mitosis.

Ubiquitylation

The post-translational covalent attachment of ubiquitin chains to targeted cellular proteins, acting as a molecular signal for their destruction in proteasomes.

Wee1

An inhibitory kinase that phosphorylates Cdk to keep the cyclin-Cdk complex in an inactive state.

Cdc25

An activating phosphatase that removes inhibitory phosphates from Cdk, triggering the rapid activation of the cyclin-Cdk complex.

p27

A Cdk inhibitor protein that physically binds to cyclin-Cdk complexes to block their assembly or enzymatic activity.

Mitogens

Extracellular chemical signals secreted by neighboring cells that stimulate the synthesis of G1 and G1/S cyclins to promote entry into the cell cycle.

Retinoblastoma (Rb) protein

A nuclear regulatory protein that restrains cell proliferation by sequestering transcription factors until it is inactivated by G1-Cdk and G1/S-Cdk phosphorylation.

p53 protein

A transcription factor that accumulates in response to DNA damage to induce p21 expression or trigger apoptosis; its gene is mutated in almost $50\%$ of human cancers.

p21

A Cdk inhibitor protein expressed downstream of activated p53 that inactivates G1/S-Cdk and S-Cdk complexes, arresting cells in G1 following DNA damage.

Origin Recognition Complex (ORC)

A multi-protein complex stably bound to DNA replication origins that recruits Cdc6 to establish replication competence.

Cdc6

A regulatory protein transiently recruited by the ORC during G1 that helps load DNA helicase to assemble the prereplicative complex (preRC).

Prereplicative complex (preRC)

A multiprotein assembly containing ORC, Cdc6, and DNA helicase assembled at replication origins during the G1 phase.

Centrosome

The primary microtubule-organizing center of animal cells that duplicates prior to mitosis to establish the two spindle poles.

Mitosis

The nuclear division stage of M phase wherein replicated chromosomes condense and are accurately segregated into two identical nuclei.

Cytokinesis

The mechanical division of the cellular cytoplasm, organelles, and plasma membrane resulting in two distinct daughter cells.

Cohesin proteins

Protein complexes that encircle and hold duplicated sister chromatids together along their length from S phase until anaphase.

Mitotic spindle

A macromolecular structure assembled from microtubules and motor proteins that aligns and segregates sister chromatids toward opposite poles during mitosis.

Contractile ring

A cytoskeletal ring composed of actin and myosin filaments situated beneath the plasma membrane at the cell equator that constricts to complete cytokinesis.

Prophase

The initial mitotic stage where replicated chromosomes condense into distinct visible threads and the mitotic spindle begins forming between separated centrosomes.

Prometaphase

The mitotic stage characterized by the breakdown of the nuclear envelope and the dynamic attachment of spindle microtubules to chromosome kinetochores.

Bi-orientation

The symmetrical attachment of kinetochores on paired sister chromatids to microtubules emanating from opposite spindle poles.

Kinetochores

Protein complexes assembled at the centromeric region of chromosomes that serve as the binding interface for spindle microtubules.

Metaphase

The mitotic stage in which all condensed chromosomes become aligned along the spindle equator midway between the two poles.

Metaphase plate

The equatorial plane situated midway between the two spindle poles where kinetochores of all chromosomes align during metaphase.

Separase

The protease that cleaves cohesin complexes at the onset of anaphase, permitting the physical disjunction of sister chromatids.

Anaphase

The mitotic phase marked by the separation of sister chromatids and their synchronized poleward transit via kinetochore microtubule shortening and spindle pole separation.

Telophase

The terminal stage of mitosis in which separated chromosome sets reach the poles, nuclear envelopes reform, and chromatin decondenses.

Cleavage furrow

The indentation of the cell surface that develops during anaphase along the spindle equator, demarcating the division plane for cytokinesis.

Integrin phosphorylation in M phase

The biochemical modification that loosens cell adherence to extracellular matrix substrates and causes animal cells to round up prior to division.

Diploid cells

Cells containing two complete sets of homologous chromosomes ($2n$)—one maternal and one paternal—encompassing all human somatic tissues.

Haploid cells

Gametic reproductive cells (egg and sperm) harboring a single set of chromosomes ($n$) composed of a mix of maternal and paternal homologs.

Germ line

The dedicated diploid precursor cell lineage localized within the testes and ovaries that undergoes meiotic division to generate haploid gametes.

Somatic cells

All diploid body cells that construct tissues and protect germ-line cells but do not directly pass genetic sequences to subsequent generations.

Meiosis

The specialized cell division process consisting of one round of DNA replication followed by two successive nuclear divisions that reduces ploidy from $2n$ to $n$, yielding four unique haploid nuclei.