Genetics

Introduction

  • Genetics: The science that studies inheritance and the expression of inherited traits.
  • Syndrome: A distinctive group of signs and symptoms occurring together in the same condition; can be inherited (e.g., syndromes described in this chapter) or acquired (e.g., AIDS).
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Proteins and Genes

  • Proteins: Important molecules that cells use to perform their specific functions.
  • Genome: The collection of all genes in the body, with each gene encoding the information to produce one protein.
  • Cellular Mechanism: Each cell in the body that has a nucleus contains the entire genome in its DNA code.
    • Cells reference the gene for a required protein like looking up a recipe.
  • Metaphor: The genome is likened to an entire recipe book that describes how to create every protein in the body.
  • Focus of Genetics: Study of the genome, including:
    • How genes synthesize proteins.
    • Variability of genes among individuals.
    • Inheritance of genes from one individual to another.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Structure of the Genome

  • DNA Organization: DNA is organized and not just freely floating in the nucleus.
    • DNA is tightly wound around proteins known as histones and further compacted into thick fibers.
    • This packing minimizes space and protects DNA from damage; it can also keep some genes turned off by tightly winding them.
  • Chromatin: The combination of DNA and special proteins (histones).
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Chromosomes

  • Gene Location: Each gene resides at a specific location on one of the 23 chromosomes.
    • Observation: Chromosomes can be seen clearly under a microscope when the nucleus and cell are dividing (chromatin is densely compacted).
  • Somatic Cells: Each somatic cell in the human body contains genetic material derived equally from both parents.
    • Chromosome Count: 46 chromosomes total (23 from father, 23 from mother).
    • Diploidy: Somatic cells are described as diploid.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Inheritance of Chromosomes

  • Inheritance: We inherit two copies of the “same” chromosome, one from each parent, resulting in having two copies of each gene.
    • Chromosome structure: 46 chromosomes total in somatic cells; Germ cells contain 23 chromosomes.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Sex Chromosomes

  • Autosomal vs. Sex Chromosomes: Chromosomes 1 through 22 are autosomal chromosomes; the 23rd set are the sex chromosomes.
  • Function of Sex Chromosomes: They produce proteins determining the sex of the fetus.
    • Types: X and Y chromosomes.
    • Males: XY (inherit Y from father’s sperm and X from mother's ova).
    • Females: XX (inherit X from both parents).
  • X Chromosome Dosage Issue: Females have twice as many X genes as males, leading to potential overexpression.
    • X Inactivation: One X chromosome in females is randomly inactivated during early embryonic development, forming a Barr body.
    • Barr Body: A dense, inactive X chromosome structure visible only in female cells.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Mitosis

  • Function: To create exact copies of each chromosome and distribute them to daughter cells.
  • Stages: Mitosis consists of four stages:
    1. Prophase
    2. Metaphase
    3. Anaphase
    4. Telophase
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Meiosis

  • Germ Cell Generation: Germ cells differ from somatic cells in chromosome number (23 chromosomes).
    • Fertilization: During fertilization, the fusion of germ cells creates a total of 46 chromosomes (23 from each parent).
    • Each gene in the offspring has one allele contributed by each parent.
  • Meiosis Process: Germ cell division occurs via meiosis, consisting of two stages:
    • 1st Meiosis: Initial division; generally involves extended prophase until ovulation.
    • 2nd Meiosis: Follow-up division.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Nondisjunction

  • Definition: Nondisjunction occurs when chromosomes fail to separate correctly during the 1st Meiosis.
    • Leads to a germ cell with an extra chromosome.
    • If this cell contributes to an embryo, it results in trisomy.
  • Example: Down syndrome (trisomy 21) includes three copies of chromosome 21 instead of two.
  • Prevalence: More common in female oogenesis than in male spermatogenesis due to prolonged crossing over; older maternal age increases trisomy risk.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Making Proteins From Genes

  • When cells require more of a specific protein, they access the genome to locate the gene responsible for producing that protein.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

RNA

  • Purpose of RNA: Transcribes the genetic code from DNA to produce amino acids, polypeptides, and proteins.
  • Types of RNA: Three types relevant to genetics include:
    • Messenger RNA (mRNA): Carries the DNA code from the nucleus to the cytoplasm.
    • Ribosomal RNA (rRNA): Forms the structure of ribosomes and aids in protein synthesis.
    • Transfer RNA (tRNA): Transfers specific amino acids to the ribosome during protein synthesis.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Genes and Alleles

  • Humans possess two copies of each gene, located at the same position (locus) on paired chromosomes.
  • Alleles: Different copies of the same gene, one inherited from each parent.
    • Example: A child could inherit a blue eye allele from one parent and a brown eye allele from the other.
  • Heterozygote vs. Homozygote:
    • Heterozygote: Different alleles (e.g., blue/brown).
    • Homozygote: Same alleles (e.g., blue/blue).
  • Dominance: Brown eye color (allele) is dominant; blue is recessive.
    • Phenotype: Physical manifestation of genetics; the phenotype of a heterozygote with brown/blue alleles will be brown eyes.
  • Recessive Phenotype: Requires a homozygous condition with the recessive allele (e.g., blue/blue).
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Patterns of Inheritance

  • Dominant Genes: Require only one copy for expression of the phenotype.
  • Recessive Genes: Require two copies for expression.
  • Inheritance Patterns: Include four major styles:
    1. Autosomal dominant
    2. Autosomal recessive
    3. X-linked dominant
    4. X-linked recessive
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Chromosomal Abnormalities

  • Categories: Chromosomal abnormalities can be divided into:
    1. Gross abnormalities (large structural changes detectable under a microscope).
    2. Molecular alterations (occurring at the DNA level, not visible microscopically).
  • Mutations: Most inherited disorders are molecular alterations or mutations that can affect one or both allelic genes.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Gross Chromosomal Abnormalities

  • Karyotype: A photographic representation of an individual's chromosomal configuration; used to observe gross chromosomal alterations.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Types of Gross Chromosomal Abnormalities

  • Alterations in Chromosome Number: Primarily due to nondisjunction.
    • Euploid: Total of 92 chromosomes (incompatible with life).
    • Polyploid: Three (triploid) or four (tetraploid) complete sets of chromosomes (also incompatible with life).
    • Aneuploid: Extra or fewer copies of a particular chromosome.
  • Structural Alterations:
    • Deletion: Loss of a portion of a chromosome.
    • Translocation: A piece of a chromosome attaches to another chromosome.
    • Inversion: A portion is flipped, reversing its order.
    • Duplication: A chromosome region is duplicated, enlarging the chromosome.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Penetrance and Expressivity

  • Penetrance: The percentage of individuals with a specific gene who display the associated phenotype.
    • 100% Penetrance: Anyone with the affected gene shows the condition.
    • Lack of Penetrance: Some individuals carry the gene but do not exhibit clinical manifestations, potentially due to modifying genes.
  • Expressivity: The degree of effect observed in individuals with the same genetic condition; can vary (variable expressivity).
    • Example: Two patients with the same genetic disorder may have different symptom intensities (e.g., peg laterals).
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].

Lyon Hypothesis and X-Linked Recessive Traits

  • X Inactivation: During early embryonic development, one X chromosome in females is genetically cancelled,
    • This cancellation impacts X chromosomes from both maternal and paternal lines.
  • Classic Hemophilia (Hemophilia A): An X-linked recessive condition characterized by blood coagulation issues due to low levels of factor VIII.
    • Males with the affected gene have a severe defect, while female carriers are mosaics, possessing both normal and affected X chromosomes.
    • The levels of factor VIII in female carriers can vary depending on which X chromosome remains active.
    • Despite being less severe than males, female carriers may experience increased bleeding tendencies, particularly after dental procedures.
    • Other related examples include different types of X-linked conditions, such as Amelogenesis Imperfecta and Hypohidrotic Ectodermal Dysplasia.
  • Reference: Ibsen, Olga. Oral Pathology for the Dental Hygienist. Available from: Elsevier, (8th Edition). Elsevier - Evolve, [2023].