Comprehensive Notes on Genetic Conditions of Health and Development

Genetic Conditions of Health and Development

Introduction to Genetics

Genetics Defined:
- The study of heredity (WHO definition).
- The study of genes (NCBI definition).
- From Greek "γένεσις" (genesis) meaning origin.

Genomics

The analysis of an organism's genome, including its sequence and internal dependencies/interactions.

Historical Milestones in Genetics

1866: Mendel's laws of inheritance.
1906/1909: Introduction of the terms "genetics" and "gene" (Bateson/Johannsen).
1910: Linking genes to chromosomes (Morgan).
1944: Discovery of DNA (Avery, McLeod, and McCarty).
1953: Identification of DNA structure (Watson and Crick).
2001 (2022): Human Genome Project - sequencing the human genome (Celera Genomics).
2015: Introduction of CRISPR - enabling DNA editing.

Modern Genetics and Genomics

Characterized by rapid technological advancement and decreasing costs.
Costs of sequencing have dramatically decreased, following a trend similar to Moore's Law.

Fields within Genetics

Classical Genetics: Study of inheritance at the individual level.
Population Genetics: Study of inheritance at the population level.
Molecular Genetics: Study of inheritance at the molecular level.
Behavioral Genetics: Study of the inheritance of behavioral traits.

Basic Genetic Concepts

Gene:
- Basic physical and functional unit of heredity.
- Transmits information from generation to generation.
- A fragment of DNA consisting of a transcribed region and regulatory sequences that enable transcription.
Chromosome:
- Form of DNA organization in living organisms.
- Contains a short arm and a long arm, separated by a centromere.
Chromosomal Location of a Gene:
- Genes are located at specific bands and sub-bands on chromosomes.
- Example: CFTR gene location - 7q31.2 (chromosome 7, long arm, region 3, band 1, sub-band 2).
Number of Chromosomes vs. Amount of Genetic Material
- $n$ - number of chromosomes
- $c$ - number of DNA molecules
- The number of chromosomes is not always equal to the number of DNA molecules.
Karyotype:
- Complete set of chromosomes in a somatic cell of an organism.
Locus (pl. loci):
- The specific location of a gene on a chromosome (or genome).
- Each gene has a specific location in the genome, however, there are exceptions with transposable elements.
Transposons:
- "Jumping genes".
- Can be retrotransposons (copy and paste mechanism) or DNA transposons (cut and paste mechanism).
- Retrotransposons involve transcription to RNA, reverse transcription, and then integration.
- DNA transposons involve excision from the donor site and integration into a new site.
Allele:
- An alternative form of a gene at a particular locus.
- Example: ABO gene has different alleles determining blood type.
Heterozygosity:
- Presence of different alleles at a given locus on each chromosome of a pair.
Homozygosity:
- Presence of the same alleles at a given locus on each chromosome of a pair.
Genotype:
- Combination of alleles at a specific locus, or the genetic constitution of an individual.
Phenotype:
- The observable characteristics of an individual.
- Phenotype is determined by genotype.
- Example: Blood type A is the phenotype resulting from AA or AO genotypes.

Heredity and Inheritance

Heredity:
- The reproduction of structure, function, and specific traits in successive generations of the same species.
Inheritance:
- The totality of genetic mechanisms determining the succession of organisms in successive generations.

Types of Cells

Somatic Cells:
- Diploid.
- Created through mitotic divisions.
Germ Line Cells:
- Diploid.
- Undergo meiotic divisions to form reproductive cells.
Gametes:
- Haploid.

Cell Cycle

Interphase:
- G1 (Gap 1): Cell grows, produces RNA and proteins.
- G0 (Resting): Cells may exit the cycle and enter G0, where they grow and differentiate but do not divide (e.g., neurons).
- G1 Checkpoint: Checks for cell size and suitable environment; if conditions are met, the cell proceeds to S phase.
- S (Synthesis): DNA is replicated, and centrioles divide.
- G2 (Gap 2): Cell continues to grow and produce new proteins.
- G2 Checkpoint: Checks for successful DNA replication, cell size, and suitable environment; if conditions are met, the cell proceeds to mitosis.
Mitosis (M):
- Prophase: Nucleolus fades, microtubules assemble into the mitotic spindle, chromatin condenses into chromosomes (each with two identical chromatids).
- Prometaphase: Nuclear membrane breaks down, spindle fibers attach to kinetochores on the chromosomes.
- Metaphase: Spindle fibers align chromosomes at the center of the cell.
- Metaphase Checkpoint: Verifies correct chromosome alignment before proceeding to anaphase.
- Anaphase: Spindle fibers shorten, kinetochores separate, and chromatids move to opposite poles.
- Telophase: Daughter chromosomes arrive at poles, spindle fibers disappear, and new nuclei form.
- Cytokinesis: Remaining spindle fibers break down, and contractile ring cleaves the cell into two daughter cells.
Meiosis( 2N Diploid cell):
- (Prophase I):
  - Chromosomes replicate into TETRAPLOID (4N) DNA as identical sister chromatids (DYADS).
  - Dyad pairs align to create TETRADS.
  - CROSSING OVER (trading of DNA) occurs at CHIASMAS between non-sister chromatids.
  - LEPTOTENE: Replicated chromosomes condense.
  - ZYGOTENE: Synapsis begins, bivalent forming, synaptonemal complex forming.
  - PACHYTENE: A bivalent has formed and crossing over has occurred.
  - DIPLOTENE: Synaptonemal complex dissociates, Chiasma occurs.
  - DIAKINESIS: Nuclear membrane fragmenting, end of prophase I.
- (Metaphase I):
  - SPINDLE FIBERS attach to each dyad at the KINETOCHORE.
  - Tension from spindle fibers aligns the tetrads at the cell equator.
- (Anaphase I):
  - Chiasmata break apart.
  - Sister chromatids begin to migrate toward opposite poles.
- (Telophase I (1N)):
  - CLEAVAGE FURROW forms beginning the process of CYTOKINESIS.
  - The result is 2 daughter cells with HAPLOID (1N) chromosomes and DIPLOID DNA (2N).
- (Prophase II):
  - Spindle formation begins.
  - Centrosomes begin moving toward poles.
- (Metaphase II):
  - Tension from spindle aligns chromosomes at the metaphase plate.
- (Anaphase II):
  - CHROMATIDS separate & move to opposite poles.
- (Telophase II):
  - CLEAVAGE FURROW forms beginning CYTOKINESIS.
  - Gamete (1N):
    - NUCLEAR ENVELOPES form.
    - Chromosomes disperse as CHROMATIN.
    - Each of the 4 gametes has 1N chromosomes & 1N DNA.
Gamete Formation:
- Spermatogenesis:
  - Male Gametogenesis
  - Spermatogonia
  - Spermiogenesis
  - interphase G³ (4c, 2n)
  - crossing over
  - interphase S (2c x 2 = 4c, 2n)
  - DNA duplication
  - prophase I (4C, 2n)
  - primary spermatocytes
  - Metaphase I (4c, 2n)
  - Anaphase I (2c, n + 2c, n)
  - Telophase I(2c, n + 2c, n)
  - Cytokinesis (c, n)
  - secondary spermatocytes
  - prophase II(c, n + c, n)
  - metaphase II (c,n)
  - anaphase II(c,n+c, n)
  - telophase II (c, n+cn)
  - spermatids
- Oogenesis:
  - Female Gametogenesis
  - mature oocyte
  - primordial oocyte
  - interphase G2 (4c, 2n)
  - crossing over
  - interphase G¹ (2c, 2n)
  - interphase S (2c x 2 = 4c, 2n)
  - DNA duplication
  - prophase I (4c, 2n)
  - Metaphase I (4c, 2n)
  - Anaphase I (2c, n + 2c, n)
  - Telophase I (2c, n + 2c, n)
  - ovulation (2c, n)
  - prophase II (2c, n)
  - metaphase II (2c, n)
  - Anaphase II (c, n + c, n)
  - telophase II (c, n + c, n)
  - polar body

Examination Details

The exam will be a test with 30 questions.
Each question will have only one correct answer.