PSYC 3102: Introduction to Behavioral Genetics
Tuesday 10/02/01
Aldehyde Dehydrogenase 2 (ALDH2) Deficiency
- ALDH2 deficiency is not a disease, it is a Mendelian Trait
- ingested alcohol is metabolized in the liver
ADH
ALDH
ethanol ----------> acetaldehyde ------------> acetic acid
ADH=alcohol dehydrogenase
- people with ALDH deficiency do not have enough of the enzyme, creating a metabolic block
- acetaldehyde builds up when they drink
- symptoms include:
vasodilation – turn red (flushing response)
nausea, vomiting
weak knees, sweating
- as a result, people with ALDH2 deficiency do not drink much and are at low risk for alcohol
abuse/dependence
it is not a 100% protective factor, a few people can and do become alcoholics
- ALDH2 deficiency is a partially dominant trait
1 good/1 bad blueprint – still have significant protection against alcoholism
A – normal allele
AA – usual risk
A – deficiency
Aa – protection
Aa – strong protection
The majority of aa people do not develop alcoholism
- ALDH2 is a tetramer of 4 identical polypeptide chains
if Aa, ½ of chains are normal, ½ have deficiency
only 1/16 ALDH2 molecules get 4 good chains
1 bad chain causes the enzyme not to work
- only found in Asian (particularly East Asian) populations
- this is a gene that influences substantive human behavior, but is not expressed in the CNS
- studies of people with this deficiency show gene-culture interaction
studies by Tu & Israel
examined East Asian immigrants into Toronto/New York areas
genotyped them for ALDH2 deficiency and kept track of their drinking
lots
ALDH
+ amount of
alcohol
consumed
ALDH
+
0
parental
generation
offspring
there was little difference between ALDH + or – parental immigrants, none drank very
much
there was a large difference in their offspring between ALDH + and –
reasons:
immigrants drank only on special occasions (weddings, funerals, etc.)
there are not many bars in rural Asia, so not part of their culture to drink much
their kids drank like other Americans/Canadians
the genotypes did not change from parents to offspring (many of the kids were born in
Asia, immigrated when very young) and raised as Americans/Canadians
- this is the best example that influences substantive behavior
it is prevalent in some populations
the action of the gene can be traced
the mutation has been identified and characterized
Fragile X Syndrome
- got its name because under the microscope part of the X chromosome of affected individuals
looked like it was breaking off
but this is not the actual cause of the syndrome
- symptoms:
long face, prominent ears (most affected, but not all)
other physical symptoms
mental retardation
hyperactivity (many diagnosed with ADHD – attention deficit hyperactivity disorder)
behavior problems (eg. conduct disorder)
- variable expressivity is strong
IQ distribution is much like for PKU (some affected individuals in normal range)
- gene located on the X chromosome – FMR1 (fragile mental retardation 1)
many more males than females with the disorder
females protected by normal allele
- mechanism of the disorder is an abnormal number of trinucleotide repeats – CGG
- gene codes for a protein that helps make other proteins
- CGG repeats in the promoter region
there is a normal range of number of repeats
when the number of repeats gets too big, it gets methylated
this turns the gene off, and reduces transcription
reduced transcription leads to reduced FMR1 protein
- trinucleotide repeats are also responsible for Huntington’s disease
- transmission of Fragile X exhibits a phenomenon called anticipation (also called Sherman’s
paradox)
anticipation = the disorder gets worse as you move down the pedigree
the current generation is affected more severely than the preceeding
- permutation – phenotypically normal, but high probability of elongating (is hypermutable)
mutation rate becomes 1/10 (compared to normal rate of 1/10,000)
increased chance of offspring with Fragile X
- the same is true of Huntington’s disease – earlier onset, greater severity with later generations
- Fragile X is the most common Mendelian disorder associated with mental retardation
Sickle Cell Anemia
- recessive disorder that influences the  chain of hemoglobin, whose role is to carry oxygen and
is made of 2  and 2  chains
- a single nucleotide change alters a single amino acid, which messes up the folding of the
protein
- messed up folding causes molecules to line up differently, causing blood platelets to be shaped
like sickles rather than plates
- cells are not always sickled – go in and out and often sickling is caused by low oxygen
conditions
- sickled cells are destroyed, causing anemia, which causes a whole host of downstream effects
- sickled cells get stuck in capillaries, depriving target tissues of oxygen, causing them to die
slowly (necrosis), which is often fatal by adolescence
- there is a geographic distribution of sickle cell anemia
certain areas of Africa (Equatorial) have high rates – 1/100
usually lethal Mendelian disorders, particularly when lethality occurs before reproductive
age
maps onto geographic distribution of a form of malaria spread by mosquitos
- turns out that carriers (heterozygotes) have resistance to malaria, which cause a reproductive
advantage because they don’t die of malaria before having kids
- Lessons:
1. the sickle-cell allele is not limited to Africa – there are high frequencies in Africa,
Middle East, and India
2. there are areas of Africa virtually free of the sickle-cell allele (virtually unheard of in
the mountains of Ethiopia)
3. highest correlation with sickle-cell anemia is malarial ecology
there is a tendency to associate it with race and ethnicity (African)
highest correlation with skin color is also ecology – distance from the equator
4. the reason we associate this syndrom with race is a historical accident
the slave trade originated from malarial areas of Africa, so many slaves had the
disease
this caused a perceived association between Africans and sickle-cell anemia
probably would have associated it with Indians if slaves had come from India
the disease really has nothing to do with race or ethnicity, but we see it as such
because of the ecological distribution
many traits are influenced by ecology