Genetics Lecture 6, 9/10: H substance, Lethal alleles

Here is the audio (if you see a time in parenthesis, it indicates that you can find that specific content at that point in the recording.)

• • A second gene that’s involved in blood type.
• o H substance. The majority of the population has the H substance.
• o You produce a gugar that is linked to galactose that is linked to fructiose linked to N acetylglucosamine. It then secretes the sugar onto the surface of the red blood cell.
• o The Ia ib allele code for enzymes that cleave the H substance to make the respective antigens (A and B)
• o People with the O blood type just have the original H substance.
• o 1952 Bombay there was a women test for the A and B antigen. She came back O. However, one of her parents is AB. Genotypically this is not possible. This person can only be A, B, or AB. It was discovered that her genotype was B → how do you get the O phenotype. She had a rare recessive mutation for the H locus. Recessive individuals do not secrete the sugar molecule. Because of this they cannot produce the A or B antigens (ending up phenotypically O).
• o The Parents (8:20)
• • Mom – AB (heterozygous for the secreter locus)
• • Dad – BO (heterozygous for secreter locus)
• • AB x BO
• ¼ AB
• ½ B
• ¼ A
• • Hh x Hh
• ¾ H_
• ¼ hh
• • ¼ AB
• ¾ H_ → 3/16 ABH_ (AB Blood type)
• ¼ hh → 1/16 ABhh (O Blood type)
• • ½ B
• ¾ H_ → 3/8 BH_ (B Blood type)
• ¼ hh → 1/8 Bhh (O blood type)
• • ¼ A
• ¾ H_ → 3/16 AH_ (A blood type)
• ¼ hh → 1/16 Ahh (O blood type
• • Results of Blood types: 6 B, 4 O , 3 A, 3 AB
• • LETHAL ALLELES
• o A number of genes which are essential to the survival of an organism. If mutate these genes . . . death of the individual with the mutation.
• o Mutant alleles can be dominant or recessive. Predominantly recessive.
• o Typically in a recessive lethal the homozygous recessive individual will die. The time of death corresponds to when that gene product is essential. Most often death occurs during embryonic period.
• o Typically heterozygotes have some phenotypical alteration.
• • Ex. Coat color in mice. Normal color grey (agouti) variant is yellow
• • Cross two agouti mice all of the offspring are agouti.
• • When you cross two yellow mice you get: 1/3 agouti and 2/3 yellow.
• • If yellow was recessive you would expect to cross two yellow mice and get 100% yellow.
• • In this case the recessive allele is lethal (22: 45)
• • AA → agouti
• • Aa → yellow
• • Aa → dead
• • Crossing two agouti mice you get all AA (agouti)
• • Cross two yellow mice
• ¼ AA → agouti
• ½ Aa → yellow
• ¼ aa → dead. Occurs during development. No live birth
• Final ratio 1/3 agouti and 2/3 yellow.
• o Dominant recessive alleles (rare)
• • Both the homozygous dominant and the heterozygote die.
• • Huntington’s disease (wildtype for the recessive trait(35:20)) – caused by a homozygous dominant allele. Onset of the disease occurs in the early 40’s
• • Mom hh. Dad Hh
• • Affected individual has offspring with unaffected individual then 50% of the offspring end up with the disease.
• o (36:00)Mice – two yellow (agouti is dominant) mice where recessive is lethal. Second trait is Fat vs. Skinny. Fat is dominant. Normal mendelian inheritance.
• o Yellow (Aa), fat (FF) x yellow, fat
• o Aa x Aa
• • ¼ agouti
• • ½ yellow
• • ¼ dead
• • SO 1/3 agouti and 2/3 yellow
• o Ff x Ff (3/4 F_ and 1/4ff)
• • ¼ FF
• • ½ Ff
• • ¼ ff
• o 1/3 agouti
• • ¾ fat = 3/12 agouti, fat
• • ¼ skinny = 1/12 agouti skinny
• o 2/3 yellow
• • ¾ fat = 6/12 yellow, fat
• • ¼ skinny = 2/12 yellow, skinny
• • Phenotypes affected by more than one Gene (42:35)
• o Mendels work was based on the idea that you have a single gene and it is passed on. There are times when two gene products interact to create a phenotype. This doesn’t necessarily mean that the proteins interact.
• o Oftentimes one gene product can mask a second gene product. Often cellular processes are linear. They are referred to epistasis interactions.
• o Example of epistasis (Bombay phenotype)
• • H locus is epistatic to the ABO blood locus
• • If an individual is Hh this will mask the genotype at the ABO locus. hh AO genotype → phenotype → O blood type.