Lecture Flashcards: Morphology of Chromosomes, Genetic Testing, and Complex Diseases

A comprehensive set of flashcards covering lecture topics on chromosome morphology, types of DNA damage and repair, Mendelian and complex inheritance patterns, genetic screening techniques, and the molecular basis of cancer.

How are chromosomes described and when do they become visible?

Chromosomes are rod-shaped, filamentous bodies present in the nucleus that become visible during cell division; they serve as carriers of units of heredity called genes.

What four types of chromosomes are differentiated based on centromere location?

Metacentric, submetacentric, acrocentric, and telocentric.

Which specific group of human chromosomes are the smallest acrocentric chromosomes and include satellites?

Group G, which includes chromosomes 21, 22, and the Y chromosome (though Y is submetacentric).

What are the secondary constrictions in acrocentric chromosomes known as, and what do they contain?

They are known as the Nucleolar Organizing Region (NOR) and contain the loci for ribosomal RNA (rRNA) genes.

Contrast the staining and gene content of euchromatin and heterochromatin.

Euchromatin is light-stained, rich in genes, and transcriptionally active; heterochromatin is dark-stained, contains few or no genes (mostly repetitive DNA), and is transcriptionally inactive.

What is Lyonization?

The random inactivation of all but one X chromosome in the cells of the blastocyst (around the 16th day of embryonic life) to form a condensed Barr Body.

Distinguish between constitutive and facultative heterochromatin.

Constitutive heterochromatin remains permanently in the heterochromatic stage (e.g., centromeres and telomeres), while facultative heterochromatin can change its condensation state and transcriptional activity depending on the cell type or developmental stage (e.g., X-chromosome inactivation).

What are the functions of centromeres and telomeres?

Centromeres are required for the segregation of chromatids during meiosis and mitosis; telomeres provide terminal stability to the chromosome and ensure its survival.

Define 'Idiogram' in chromosomal analysis.

An arrangement of chromosomes according to their sizes from large to small, with the short arm up and centromeres aligned in one row.

What is the standard notation for a normal female and normal male karyotype?

Normal female: $46,XX$; Normal male: $46,XY$.

What chemical is used in karyotyping to inhibit the assembly of microtubules and stop mitosis?

Colcemid (or Colchicine).

Which DNA repair pathway is defective in Xeroderma Pigmentosum (XP)?

Nucleotide Excision Repair (NER), which removes bulky, helix-distorting lesions like UV-induced thymine dimers.

What condition is associated with a defect in DNA Mismatch Repair (MMR)?

Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer – HNPCC).

Explain the difference between silent, nonsense, and missense mutations.

Silent: No change in amino acid. Nonsense: Converts an amino acid codon into a stop codon. Missense: Replaces one amino acid with a different one.

What enzyme system converts superoxide radicals into hydrogen peroxide, and which one converts hydrogen peroxide into water?

Superoxide dismutase converts superoxide radicals to hydrogen peroxide; Catalase converts hydrogen peroxide to water.

What is the 'Threshold Model' in multifactorial inheritance?

A model where a disease manifests only when the combined genetic and environmental liability exceeds a certain level.

Define 'Anticipation' in genetic disorders.

The tendency for some genetic disorders (like Huntington disease or Fragile X syndrome) to manifest at an earlier age or increase in severity with each succeeding generation, often due to trinucleotide repeat expansion.

Contrast Prader-Willi Syndrome and Angelman Syndrome regarding genomic imprinting.

Prader-Willi results from the loss of the active paternal allele (maternal is inactivated), while Angelman results from the loss of the active maternal allele (paternal is imprinted/silenced) in the chromosome $15q11q13$ region.

What are the molecular markers used in prenatal first-trimester screening for Down Syndrome?

Low PAPP-A (pregnancy-associated plasma protein A), high free $\beta \text{-hCG}$ (human chorionic gonadotrophin), and increased Nuchal Translucency (NT) on ultrasound.

What is the 'Philadelphia Chromosome' and its clinical association?

A reciprocal translocation $t(9,22)$ that fuses the BCR and ABL1 genes into a hybrid oncogene, causing Chronic Myelogenous Leukemia (CML).

What role does the p53 protein play in cell cycle control?

Known as the 'Guardian of the Genome,' it monitors DNA integrity, induces G1/S arrest to allow repair, or triggers apoptosis if damage is irreparable.

Define 'Phenocopy' with an example.

An environmentally induced variation that resembles a genetically determined trait, such as cataracts caused by Rubella virus infection in utero mimicking inherited cataracts.

What is the difference between genetic sensitivity and specificity?

Sensitivity is the ability to detect affected individuals (low false negatives); specificity is the ability to correctly identify unaffected individuals (low false positives).

What does the presence of red vs. green spots on a DNA Microarray indicate in cancer research?

Red spots indicate genes that are more expressed in cancer cells (upregulated); green spots indicate genes that are more expressed in normal cells (downregulated in cancer).

What is the clinical hallmark of Ataxia Telangiectasia?

Impaired movement (ataxia) and small, dilated blood vessels (telangiectasia) visible in the eyes or on the skin, caused by mutations in the ATM gene.