Genetics 3.2 - After test

• Influence of both alleles in a heterozygote is clearly evident
• co-dominance - the joint expression of both dominant and recessive alleles
• •Karl Landsteiner and Philip Levin

       - Glycoprotein molecule found on the

         surface of red blood cells

       - acts like native antigen

       - exists in two forms; M and N

       - gene to produce this glycoprotein is in  

                 Chromosome # 4
• Incomplete dominance - When not enough of an enzyme is produced, and the dominant allele isn’t completely dominant over the recessive allele.
• Multiple alleles

  • All genes - 2 segregating alleles
  • Human blood group gene - 3 alleles, A B and O
  • Karl Landsteiner - early 1900s
  • A and B antigens are different from M and N
  • Genes for the A and B antigens are in chromosome #9
• A - produces A antigen

  B - produces B antigen

  O- produces no antigens
• The A alleles is responsible for an enzyme that can add the terminal sugar N-acetylgalactosamine (AcGalNH) to the H substance.

   The IB allele is responsible for a modified enzyme that cannot add  N-acetylgalactosamine but instead can add a terminal galactose. 

  The O phenotype results from an absence of either terminal sugar
• PKU - Phenylketonuria

  • People lack enzymes necessary for the normal metabolism of the amino acid phenylalanine to the next product.
  • Phenylalanine accumulates
  • Low IQ
  • Small head size
  • Hair color
• Phenylalanine is a sleeping agent. Things that contain it - aspartame, diet soda, meat, proteins, turkey, peas, beans
• Marfan syndrome

  • Autosomal dominant mutation causes this defect
  • Coding the connective tissue protein fibrillin
  • Needed for the structure of the len of the eye, bones, lining vessels of aorta
  • Lens dislocation
  • Increased risk of aortic aneurysm
  • Lengthened bones in limbs
  • Abe lincoln
• Porphyria variegata

  •  cannot adequately metabolize porphyrin component of hemoglobin -breaks down
  • Accumulation of porphyrin can be seen in urine – red colored urine
  • It can build up in the body and brain
  • Leads to cause: abdominal pain, muscular weakness, fever, insomnia, headache, vision problems, convulsions.
  • Historical importance:

      - King George III, King of England – suffered from this disorder
• Conditional alleles: only work at certain conditions

  • Fruit flies: alleles of number of genes may be lethal at temps above 28C, with no effect at lower temps
  • Primroses: red flowers at 24C and white above 32C
  • Siamese cats and himalayan rabbits: darks color in paws ear and nose at lower body temp, higher temp = light color
• Some alleles can be lethal, such as coat color in mice.
• The mutant alleles always on (gain of function); deletion affects neighboring essential gene for development of embryo
• Mutation may sometimes be tolerated in the hetero state, but is lethal when it’s homo

  The lethal allele when homo, can result in a distinctive mutant phenotype when hetero. The alleles behaves as a lethal recessive, but dominant in phenotype
• In some cases, a mutation can be a dominant lethal allele, in which the heterozygote won’t survive. Ex. huntington disease
• Nutritional effects:

  • Prototroph – Anyone who can produce all the necessary enzymes for production
  • Autotroph – A mutation where an enzyme isn’t produced to digest food
  • Phenylketonuria – An allele is unable to produce an enzyme that breaks down phenylalanine
  • Galactosemia – Individuals have 3 genes/enzymes to break down lactose sugar, but with galactosemia, an individual is unable to breakdown galactose
  • Lactose intolerance – no alleles to produce enzymes to break down lactose
• •Modifier genes – alleles at other genes may influence the penetrance and expressivity of a gene.ex. Intensity of pigmentation when homozygous(for a gene)

  • Phenocopy: Environmental factors can induce a particular abnormal phenotype that could be genetically determined. Example: 1950s and 1960s - # of babies were born with short limbs – due to rare recessive genetic disorder.  Due to sleeping pill – Thalidomide taken by pregnant mothers.
• •Some traits are not expressed at the same time during an organism’s life span!•Age becomes a factor.

     Examples:

  •Tay - Sachs disease – autosomal recessive trait – abnormal lipid metabolism – deficiency of enzyme – Hexosaminidase A;lethal lipid metabolism disease.(British opthomologist Waren Tay and American Neurologist - Bernard Sachs)

     -  newborns are normal.

     - after few months:

            - developmental retardation

            - paralysis, blindness

            - die at the age of three
• Lesch-Nyhan Syndrome

     - deficiency of the enzyme hypoxanthine-guanine phosphoribosyl-transferase (HGPRT)

     - Characterized by medical student Michael Lesch and his mentor, pediatrician William Nyhan X-linked recessive disease

  •Nucleic acid metabolism

  •Accumulation of uric acid in blood and tissues

  •Mental retardation

  •Self mutilation of lips and fingers

  •Disorder is due to – a mutation in the gene encoding for HPRT (hypoxanthine guanine phosphoribosyl transferase)•Newborns – normal for 6 – 8 months. Exclusively in males!
• •DMD – Duchenne Muscular disease

     - caused by a mutation in the dystrophin  

       gene, located on the human X 

       chromosome, which codes for the protein 

       dystrophin.

     - normal for 3-5 years ; common in Boys. Females are rarely affected

  •Huntington Disease

     - autosomal dominant disease

     - occurs between 30 -50 years age
• • X – Chromosome

  • Y – Chromosome

  • XX in females, XY in males

  • X – Linked traits

         - Color blindness

         - Females – XCXC, XCXc, and XcXc

  • Males have only one X chromosome, Two types of males are – XCY and XcY
• x-linked recessive trait

  • Example – Hemophilia

                   - Recessive allele from carrier mother

     - Yellow-green color blindness, DMD – Duchene Muscular Dystrophy, Fragile X - Syndrome

  • # of the descendants of Queen Victoria of

         England

        - She was heterozygous for this allele

  • Males are affected often

  • ¼  of the offspring are affected in each  

       generation
• x-linked DOMINANT trait

  • Both males and females are affected

  • Sometimes more females are affected

  • ½ of the offspring in every progeny is affected

  • affected males produce all affected female offspring;   

       no affected males

       Example: deafness

                    Pseudohypoparathyriodism

                    Rett’s syndrome – only in females

                    Incontinentia Pigmenti
• •Many traits characterized by a distinct phenotype are affected by more than one gene

  •In gene interaction, the cellular function of numerous gene products contributes to the development of a common phenotype
• •In epistasis, one gene’s alleles mask the effects of another gene’s alleles

  •For some traits, homozygosity for a mutant allele at one of two or more genes produces the phenotype

  •In other cases, two gene pairs complement each other such that one dominant allele is required at each locus to express a certain phenotype

  •Novel phenotypes can emerge from the combined action of the alleles of two genes
• •The term epistasis describes the situation in which a gene can mask the phenotypic effects of another gene

  •Epistatic interactions often arise because two (or more) different proteins participate in a common cellular function
• •If an individual is homozygous for either recessive allele, it will not make any functional enzyme C or enzyme P–Therefore, in the previous example, the flowers remain white