
<ul>
  <li>May be</li>
  <ul>
    <li>Abnormal structure</li>
    <li>Abnormal number (aneuploidy): most common (3-4% of all pregnancies)</li>
  </ul>
</ul>

## Aneuploidy
<ul>
  <li>Usually due to meiotic nondisjunction in meiosis I</li>
  <ul>
    <li>Gamete contains 24 chromosomes but has both copies of one pair</li>
  </ul>
</ul>

## Chromosome structural defects
<ul>
  <li>Structural abnormalities result from chromosomal breakage</li>
  <li>Can be</li>
  <ul>
    <li>Balanced: normal amount of information</li>
    <ul>
      <li>
        These don&rsquo;t usually cause an abnormal phenotype but can create a carrier status with
        unbalanced gametes and problems for future generations
      </li>
    </ul>
    <li>Unbalanced: additional or missing information</li>
  </ul>
  <li>Single breaks may be repaired</li>
  <li>Multiple breaks may lead to random rejoining of incorrect ends</li>
  <li>Triggers for breakage</li>
  <ul>
    <li>Chemicals</li>
    <li>Ionizing radiation</li>
  </ul>
  <li>Examples</li>
  <ul>
    <li>Translocation (balanced): exchange of segments between non-homologous chromosomes</li>
    <ul>
      <li>
        Robertsonian translocation: breaks occur near the centromere in two acrocentric chromosomes.
        The short arms are lost but generally this is not damaging. In this case the karyotype is 45
        chromosomes (one being a combination of two)
      </li>
    </ul>
    <li>Inversion (balanced): segments are inverted in sequence</li>
    <ul>
      <li>Requires at least two breaks with the intervening segment being inverted 180 degrees</li>
      <li>If involves centromere: pericentric</li>
      <li>If within an arm: paracentric</li>
    </ul>
    <li>Deletion (unbalanced): segments are lost</li>
    <ul>
      <li>Phenotype depends on size of lost segment and its function</li>
    </ul>
    <li>Duplications (unbalanced): tend to be less harmful</li>
    <li>Ring chromosomes (unbalanced): two breaks occur and the two ends unite</li>
    <li>Isochromosomes (unbalanced): one arm is missing and the other is duplicated</li>
  </ul>
</ul>

## Gene mutations
<ul>
  <li>Can range from a single base pair to deletion of large segments</li>
  <li>Point mutation (nucleotide substitution)</li>
  <ul>
    <li>
      Missense mutation: different amino acid is transcribed, altering the &ldquo;sense&rdquo; of
      the code (eg. haemoglobinopathies)
    </li>
    <li>
      Nonsense mutation: mutation leads to a premature stop codon (eg. Neurofibromatosis type 1)
    </li>
    <li>Splice site mutation: mutation alters a critical splice junction</li>
  </ul>
  <li>Deletions and insertions</li>
  <ul>
    <li>
      Frameshifts: deletion or insertion alters the reading frame of translation leading to an
      inappropriate amino acid sequence
    </li>
    <li>
      Codon insertions/deletions (bases lost/gained in multiples of three) eg. repeat expansions
    </li>
  </ul>
</ul>
<ClinicalCorrelate>
  <p>
    Examples of triplet expansion diseases include myotonic dystrophy, fragile X (FMR-1 gene),
    Huntington&rsquo;s, spinocerebellar ataxia
  </p>
</ClinicalCorrelate>
<ul>
  <li>Gene deletions/duplications</li>
</ul>

## Contiguous gene (or micro-deletion) syndromes
<ul>
  <li>Prader-Willi</li>
  <li>Williams syndrome</li>
  <li>Di George</li>
  <li>Rubinstein-Taybi</li>
</ul>


Genetics

Chromosome Defects

Intro

FRCOphth Part 1 Study Notes

Orbit and ocular adnexae

Orbit

Extraocular Muscles

Orbital Blood Vessels

Paranasal Sinuses

Lacrimal Glands

Tear Film

Eyelids

Blinking

Anterior segment - ocular surface

Conjunctiva

Conjunctivitis

Sclera

Cornea

Corneal Structure And Development

Corneal Physiology

AC to Lens

Angle

Ciliary Body

Aqueous Humour Dynamics

Iris

Pupil

Lens

Posterior segment

Choroid

Vitreous

Retinal Macrostructure

Neurosensory Retina

Retinal Pigment Epithelium

Neuroanatomy

Venous Sinuses

Cerebral Ventricles

Cerebral Blood Supply

Supranuclear Gaze Pathways

Head And Neck Autonomic Nervous Supply

Head And Neck Glands

Osteology

Nerves

Muscles And Pharyngeal Arches

Extraocular Nerves

Sensory Nerves

Physiology

Physics Of Blood Flow

Neuronal Control Of Blood Vessels

Oxygen-Haemoglobin Dissociation Curve

Cytochrome p450

Pituitary Gland

Thyroid Hormone Production

Insulin

Glucagon

Parathyroid Hormone

Corticosteroids

Catecholamines

Cardiac Cycle

Renal Physiology

Fluid Balance

Acid-Base Balance

Muscle Physiology

Sensory Fibres

Cutaneous Receptors

Endocytosis

Glycosaminoglycans

Condensed Ocular Biochemistry

Eye Movements

Accomodation

Vision

Visual Cycle And Phototransuction

Visual Pathway

Visual Acuity

Colour Vision

Binocular Vision

Pathology

Collagen

Tissue Damage

Inflammation

Disease Entities

Wound Healing

Thrombosis / Atherosclerosis

Cell Growth

Neoplasia

Histopathology

Nystagmus

Free Radicals And Antioxidants

Immunology

Ocular Immunology

Microbiology

Viral Infections

Bacterial Infections

Fungal Infections

Protozoa

Nematodes

Antimicrobials

Chromosomes

Mitosis

Meiosis

Genes

Polypeptide Synthesis

Histones

MicroRNA

Hardy-Weinberg Equilibrium

Mutations

Autosomal Inheritance

X-Linked Inheritance

Mitochondrial Inheritance

Multifactorial Inheritance