Genetics - 3.2 After after test

• Incomplete dominance - not enough enzyme produced, the dominant allele isn’t completely dominant over the recessive allele
• Codominance - influence of both alleles in a heterozygotes is clearly evident

  • Joint expression of both dom 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 on Chromosome #4
• Human blood group gene - three alleles, A B and O

  A and B antigens are different from M and N

  Genes for A and B antigens are on chromosome #9

  • A produces antigen A
  • B produces antigen B
  • O produces no antigens
• The A allele is responsible for an enzyme that can add the terminal sugar N-acetylgalactosamine to the H substance

  The B allele is responsible for a modified enzyme that CAN’T add N-acetylgalactosamine but can instead add a terminal galactose

  The O phenotype results from an absence of either terminal sugar
• Pleiotropy - alleles that affect more than one character

  Ex. Phenylketonuria (PKU)

  • People lack the enzyme necessary for the normal metabolism of the amino acid Phenylalanine to the next product
  • Phenylalanine accumulates
  • Gene affects 1. Accumulations of phenylalanine 2. Low IQ 3. Small head size 4. Hair color
• Marfan syndrome 

  • Autosomal dominant mutation causes this defect
  • Coding the connective tissue protein fibrillin
  • Needed for the structure of the lens of the eye, bones, lining vessels or aorta
  • Lens dislocation, increased risk of aortic aneurysm, lengthened bones in limbs, Abe lincoln possibly affected
• Porphyria variegata

  • Can’t adequately metabolize porphyrin component of hemoglobin - breaks down
  • Accumulation of porphyrin can be seen in red colored urine
  • It can build up in the body and brain
  • Leads to abdominal pain, muscular weakness, fever, insomnia, headache, vision problems, convulsion. 
  • King George III of England had this
• Conditional alleles

  Fruit flies - Alleles of number of genes may be lethal at temps above 28 C but have no effect at lower temps

  Primroses - produce red flowers at 24 C and white above 32 C

  Siamese cats and himalayan rabbit coats - darker color at the paws, ears, and nose at lower body temp, higher body temp -> lighter in color
• •Lethal allele: coat color in mice

  •Example: agouti (coat color) in mice

  –agouti x agouti à all agouti

  –yellow x yellow à 2/3 yellow, 1/3 agouti

  –agouti x yellow à ½ yellow, ½ agouti

  –Explanation: Mutant allele always on (gain of function); deletion actually affects neighboring essential gene (Merc) responsible for development of embryo
• A loss of function - mutation can sometimes be tolerated in the heterozygous state, but may behave as a recessive lethal allele in the homozygous state. In such a case, homozygous recessive individual won’t survive
• The allele responsible for a lethal effect when it’s homozygous can also result in a distinctive mutant phenotype when it is heterozygous. Such an allele is behaving as a recessive lethal, but is dominant with respect to the phenotype.
• In some cases, a mutation can be a dominant lethal allele, in which case the heterozygote won’t survive. For example, Huntington’s Disease. For the dominant lethal alleles to exist, the affected individual must reproduce before dying.
• 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. Control the function of the genes, can control if another genes turns on or not
• Phenocopy - Environmental factors can induce a particular abnormal phenotype that could be genetically determined. Ex., in the 1950s and 1960s, many babies were born with short limbs due to a rare recessive genetic disorder. This was due to the pregnant mothers taking Thalidomide, a sleeping pill
• For some genes, a given genotype may or may not show the given phenotype. The level of expression of a given genotype is expressivity
• Sometimes age affects when a trait is expressed. Ex. Tay-Sachs disease

  • Autosomal recessive trait
  • Abnormal lipid metabolism
  • Deficiency of enzyme Hexosaminidase A
  • Lethal lipid metabolism disease
  • Waren Tay and Bernard Sach
  • Newborns are normal, but after a few months they get developmental retardation, paralysis, blindness, and die at the age of 3
• Lesch-Nyhan syndrome/Kelley-Seegmiller syndrome/juvenile gout

  • Deficiency of the enzyme hypoxanthine-guanine phosporibosyl-transferase (HGPRT)
  • Characterized by medical student Michael LEsch and his mentor William Nyhan, a mutation in the gene that encodes for this enzyme
  • X-linked recessive disease
  • Nucleic acid metabolism
  • Accumulation of uric acid in blood and tissues
  • Mental retardation
  • Self mutilation of lips and fingers
  • Newborns are normal for 6-8 months
  • Exclusively in males
• DMD- Duchenne Muscular Disease

  • Caused by a mutation in the dystrophin gene, located on the X chromosome which codes for the protein dystrophin
  • Normal for 3-5 yrs, common in boys but females are rarely affected because men have only one X chromosome
• Huntington Disease

  • Autosomal dominant disease
  • Occurs between 30-50 years of age
• X-linked recessive trait. Ex. hemophilia

  • Recessive allele from carrier mother
  • Yellow-green color blindness, DMD, fragile X syndrome
• X-linked dominant trait

  • Both males and female 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
  • Ex. deafness, pseudohypoparathyroidism, rett’s syndrome (females only), incontinentia pigmenti
• Rett’s syndrome onset may be late, the mutation isn’t inherited, it occurs spontaneously on the x chromosome
• Phenotypes are often affected by more than one gene. 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. 2 genes interact to give a certain phenotype, 4 alleles total contribute to the 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 2 gene pairs complement each other such that one dom allele is required at each locus to express a certain phenotype.
• The term epistasis describes the situation in which a gene can mask the phenotypic effects of another gene

  Epistatic interactions often arise between 2 or more different proteins participate in a common cellular function
• Recessive epistasis - inheritance of coat color in mice

  Dom allele in one genetic locus masks the expression of the alleles in the 2nd locus

  Complementary gene interaction - must have at least 1 dom allele at each locus (A and B) to have the phenotype
• 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

  Quantitative traits - phenotype is determined by the number of dom and rec alleles present for different genes - polygenic. They are affected by the environmental factors and have continuous distribution
• •Sex-limited inheritance occurs in cases where the expression of a specific phenotype is absolutely limited to one sex

  •In sex-influenced inheritance, the sex of an individual influences the expression of a phenotype that is not limited to one sex or the other
• Paternity exclusion: •HLA Haplotypes:

       Human Leucocytes Antigen

       (blood group enzymes)

     - genes coding for antigen presenting proteins

       of WBC – on chromosome # 6

    - Haplotypes stay intact from generation to

      generation

    - HLA genes are close to each other on the 

      chromosome

    - HLA genes are tightly linked