Congenital _amp; Genetic Disorders

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					        Genetics
Congenital & Genetic Disorders




       Pathophysiology
              Review of Human Genetics
• Genes, diploid, alleles, traits
    – Genes = segment of DNA responsible for a particular trait
             – Gene locus = where it’s located on the chromosome
                  » Human genome project
    – Diploid = when one’s chromosomes are in matched pairs
             – One chromosome in the matched pair ---- from the father
             – One chromosome in the matched pair from the mother
             – These sister chromosomes called homologs
    – Alleles = genes that have the same locus (location) on sister chromosomes
             – Allele = each form of the same gene
    – Trait = what both alleles eventually code for
             – 2 genes(alleles) are responsible for most traits
                  » One from the mother; one from the father
• Mitosis & meiosis
    – Mitosis = process of cell replication where DNA is replicated (“mutations”)
            – For maintenance and growth of the organism
            – Chromosomes number stays constant
    – Meiosis = process of making sex cells (gametes)
            – For sexual reproduction
            – Chromosome number is reduced by half                SEE NEXT SLIDE
• MEIOSIS = nuclear division mechanism with which the
                parental chromosome number is reduced by half
               » Thus, going from a diploid cell to a haploid cell
               » purpose = to make gametes ( sex cells)
• Meiosis has 2 divisions (note that mitosis has only one division)
      1. MEIOSIS I
               » phases = Prophase I, Metaphase I, Anaphase I, Telophase I
               » called “reduction division”
               » In prophase 1, when homologs synapse --- called “tetrad” since
                 chromosomes are already in chromatid form
              » Key = Homologs separate
      2. MEIOSIS II
               » phases = Prophase I, Metaphase II, Anaphase II, Telophase II
               » called “mitotic division”
               » Key = Chromatids separate
          Special Events in Meiosis I
• CROSSING OVER
   – In Prophase I the homologs align up (i.e. synapsis)
       • Remember that each chromosome is in the chromatid form
       • non-sister chromatids exchange whole segments or individual genes where
         they touch (where they touch is called a chiasma)
       • When the homologs align, there are 4 chromatids
          that are close together
   – Key = during Prophase I , alleles are exchanged
            between homologs via “Crossing Over”
• RANDOM ASSORTMENT
   – In Metaphase I the homologs align at the spindle equator
   – they align at random
   – Thus, the male homologs & female homologs are
      interchanged at random


• Remember what genetic products are interchanged:
       • Crossing Over during Prophase I - - - - - - mixes GENES
       • Random Assortment during Metaphase I - - mixes CHROMOSOMES
  Reasons for Genetic Diversity
• [1] random fertilization
         – Mature woman ovaries = 1 million ova
         – Mature man sperm = 10 million/ ejaculate
         – Possibilities = 10 million x 1 million = 10 trillion
• [2] crossing over
         – Occurs in prophase I
         – Mixes genes
• [3] independent assortment
         – Occurs in metaphase I
         – Possibilities = for diploid organisms put 2 to the power
           determined by the haploid number of chromosomes
             » 223 = 8. 3 million
• Vocabulary
   – Dominant allele = in large case; fully expressed
            – A dominant allele masks the expression of a recessive allele
   – Recessive allele = in small case; not expressed unless both alleles are recessive
   – True breeding (same as homozygous)
            – All offspring same as parent
            – The inheritance of identical alleles for a particular trait
   – Hybrid breeding (same as heterozygous)
            – The inheritance of non-identical alleles for a particular trait
   – Trait expression
            – Homozygous dominant = pair of identical dominant alleles
            – Homozygous recessive = pair of identical recessive alleles
            – Heterozygous = pair of non-identical alleles
   – Genotype = actual genes one has for a trait
   – Phenotype = the appearance one sees for that particular trait
            – If appearance is the dominant expression you are either homozygous
              dominant or heterozygous
            – If appearance is the recessive expression you can be only homozygous
              recessive
• Inheritance pattern in humans (3 types)
    [Of 23 pairs of chromosomes: 22 = autosomes, 1 = sex chromosomes]
    – (1) Autosomal recessive
            – Commonest type of human inheritance
            – Ones gets both recessive genes for a trait
            – The heterozygote is a carrier; thus can skip generations
                » Incomplete dominance =when carrier has “a little disease” (Ss)
            – Includes:
                » Albinism
                » Sickle-cell anemia
                » Cystic fibrosis
                » Tay-Sachs disease
                » Pnenylketonuria
– (2) Autosomal dominant
       –   If have one or both dominant genes, the trait is expressed
       –   There are no carriers
       –   Can get codominance --- human ABO blood type
       –   Includes:
              » Huntington’s chorea
              » Polycystic kidneys
              » Marfan’s syndrome
              » Polydactyly
– (3) X-linked recessive
        – Clues that hint you are dealing with X-linked recessive trait
            » Males show phenotype much more than females
            » A son cannot inherit the recessive allele from his father
            » A daughter can inherit the recessive allele from her father
            » If mother a carrier– there is a 50% chance that each son will
               inherit the allele
        – Includes:
            » Color blindness
            » Hemophilia
            » Muscular dystrophy
Family pedigree for an X-linked recessive trait
             Congenital Diseases
• Def: = those diseases present at birth
                » Note that not all genetic diseases present at birth
• Congenital diseases include:
        • (1) Developmental diseases
             – Those that arise spontaneously during gestation
                 » Exp = failure of testis to descend
             – Those that are secondary to environmental problems
                 » From trauma
                 » From poisons (teratogenic agents)
                 » From poor nutrition of mother during gestation
        • (2) Genetic diseases
             – Single gene disorders --- nucleotide mutation
             – Chromosomal defects
                 » Usually occurs during mitosis
             – Multifactoral disorders
                 » Polygenic (exp = diabetes)
                 » Genetic tendency + environment (exp = lung cancer)
                Genetic Diseases
• Single gene disorders
       • Classified by inheritance pattern
• Chromosomal diseases
       • 2 types
            – Structural change of the chromosome
                 » Deletion = cause most serious problems and/or death
                 » Translocation = broken part of chromosome becomes
                   attached to non-homologous chromosome
                          * Reciprocal or non-reciprocal (see next slide)
            – Change in chromosome number
                 » Caused during meiosis by nondisjunction
                 » Euploidy = normal number of chromosomes
                 » Aneuploidy = abnormal number of chromosomes
                          * Exp = turner’s syndrome = monosomy X
                                  Down’s synd. = Trisomy 21
• Multifactoral diseases
      • May be a combination of environmental factors & genetic tendency
           – Exp = lung cancer, “not so smart” people, colon cancer
       • These may be polygenic
           – Exp = deafness, diabetes
• Genetic testing
       • Karyotype
           – Gross structure chromosomal map
       • Genome
           – Loci specific chromosomal map
       • Analyzing the genes nucleotides
       • Blood tests looking for biochemical defect
       • Amniotic fluid analysis --- looking for biochemical defect
• Down’s Syndrome
      • Called trisomy 21
      • Seen more frequently as pregnant woman get older
          – Key = age 35 when risk increases dramatically
      • Physical signs
          – Small, flat head with low-set ears
          – Slanted eyes sometimes with epicanthal fold
          – Mouth hangs open with large protruding tongue
          – Simian crease
          – Short stature
          – Space between 1st & 2nd toe
          – Short little finger

      • congenital form of mental retardation associated with other findings which
        include:
               » congenital heart defects (commonest = ASD)
      • etiology = genetic defect ( commonest = trisomy 21)
           – More common in older pregnant women
               » incidence at age 35 = 1/650
               » incidence at age 40 = 1/60
      • diagnosis = karyotype

				
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posted:8/14/2012
language:English
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