Textbooks

• Development begins with fertilization, the process by which the male gamete, the sperm, and the female gamete, the oocyte, unite to give rise to a zygote
• Primordial germ cells (PGCs)


  Cells formed in the epiblast during the second week that move to the wall of the yolk sac and then migrate to the developing gonads

  
• Mitotic divisions increase the number of germ cells during their migration and also when they arrive in the gonad
• Gametogenesis


  The process by which germ cells undergo meiosis to reduce the number of chromosomes and cytodifferentiation to complete their maturation

  
• Chromosome theory of inheritance


  Traits of a new individual are determined by specific genes on chromosomes inherited from the father and the mother
• Somatic cells


  • Chromosomes appear as 23 homologous pairs to form the diploid number of 46, with 22 pairs of autosomes and 1 pair of sex chromosomes

  
• Gametes


  Each gamete contains a haploid number of 23 chromosomes, and the union of the gametes at fertilization restores the diploid number of 46
• Mitosis


  1. Cell division giving rise to two daughter cells that are genetically identical to the parent cell

  2. Each daughter cell receives the complete complement of 46 chromosomes

  
• Meiosis


  1. Cell division in germ cells to generate male and female gametes, sperm and egg cells, respectively

  2. Meiosis requires two cell divisions to reduce the number of chromosomes to the haploid number of 23

  
• Crossover


  Interchange of chromatid segments between paired homologous chromosomes during meiosis I

  
• Polar bodies


  Three of the four daughter cells produced during meiosis of the primary oocyte, which receive little cytoplasm and degenerate

  
• Chromosomal abnormalities, which may be numerical or structural, are important causes of birth defects and spontaneous abortions
• Meiotic division


  1. Homologous chromosomes separate

  2. Nondisjunction occurs

  3. Chromosomes move into one cell

  
• Nondisjunction during meiosis can result in gametes with 24 or 22 chromosomes instead of the normal 23

  
• When a gamete with 23 chromosomes fuses with a gamete with 24 or 22 chromosomes, the result is an individual with 47 (trisomy) or 45 (monosomy) chromosomes
• Nondisjunction can occur during mitosis, resulting in mosaicism with some cells having an abnormal chromosome number

  
• Chromosomal translocations can be balanced (no critical genetic material lost) or unbalanced (part of a chromosome lost, altered phenotype)

  
• Down syndrome


  • Caused by an extra copy of chromosome 21
  • Features include growth retardation, mental retardation, craniofacial abnormalities, cardiac defects, hypotonia

  
• Trisomy 18


  • Features include mental retardation, congenital heart defects, low-set ears, flexion of fingers and hands
• Trisomy 13


  • Features include mental retardation, holoprosencephaly, congenital heart defects, cleft lip/palate, eye defects

  
• Klinefelter syndrome


  • Found only in males, features include sterility, testicular atrophy, gynecomastia, XXY chromosomes
• Turner syndrome


  • Only monosomy compatible with life, features include short stature, webbed neck, lymphedema, gonadal dysgenesis

  
• Triple X syndrome


  • Features include infantilism, scanty menses, mental retardation, two sex chromatin bodies
• Structural chromosome abnormalities can result from chromosome breakage, leading to partial deletions and associated syndromes
• Microdeletion syndromes


  • Caused by small deletions spanning a few contiguous genes, e.g. Angelman and Prader-Willi syndromes
• Fragile sites are regions of chromosomes prone to separation or breakage, with fragile X syndrome being the only one correlated with an altered phenotype
• Single gene mutations account for approximately 8% of human malformations
• Fragile X syndrome


  Characterized by mental retardation, large ears, prominent jaw, and pale blue irides
• Males are affected more often than females (1/1000 versus 1/2000) with fragile X syndrome, which may account for the preponderance of males among the mentally retarded
• Fragile X syndrome is second only to Down syndrome as a cause of mental retardation because of chromosomal abnormalities
• Single gene mutation


  A change in the structure or function of a single gene that directly causes a congenital formation in humans
• Single gene mutations are estimated to account for approximately 8% of all human malformations
• Dominant mutation


  A mutant gene that produces an abnormality in a single dose, despite the presence of a normal allele
• Recessive mutation


  A mutation where both alleles must be abnormal (double dose) or if the mutation is X-linked in the male
• Mutations in key genes in development are responsible for some congenital abnormalities and childhood diseases
• Inborn errors of metabolism like phenylketonuria, homocystinuria, and galactosemia are frequently accompanied by or cause various degrees of mental retardation
• Cytogenetic analysis


  Technique used to assess chromosome number and integrity by staining chromosomes to reveal banding patterns

  
• Fluorescence in situ hybridization (FISH)


  Technique that uses specific DNA probes to identify ploidy for a few selected chromosomes

  
• Spectral karyotype analysis


  Technique where every chromosome is hybridized to a unique fluorescent probe of a different color and analyzed by a computer

  
• Oogenesis


  1. Primordial germ cells differentiate into oogonia

  2. Oogonia undergo mitotic divisions

  3. Some oogonia arrest in prophase of meiosis I and form primary oocytes

  4. Primary oocytes enter diplotene stage of prophase and remain there until puberty

  5. At puberty, primary oocytes resume meiosis I and complete it, forming a secondary oocyte and first polar body

  6. Secondary oocyte arrests in metaphase of meiosis II until fertilization