Curse And Blessing Of The Ghetto 4b137

CURSE AND BLESSING OF THE GHETTO By Jared Diamond

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TAY-SACHS DISEASE Tay-Sach’s Disease is named after two physicians--British ophthalmologist W. Tay, and New York neurologist B. Sachs. They independently recognized the disease back in 1881 and 1887, respectively.

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TAY-SACH’S DISEASE Tay-Sach’s Disease is a rare, incurable, and unpreventable autosomal recessive genetic disorder which is caused by Hexosaminidase A (HEXA) deficiency in lysosomes. Lacking this enzyme causes excessive accumulation of the fatty substance called GM2 ganglioside in nerve cells, particular in the spinal cord and brain.

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SYMPTOMS ▹ Symptoms appear 3-6 months after birth ▹ Loss of muscle strength and control ▹ Convulsions/Seizures

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SYMPTOMS ▹ Increased startle reaction ▹ Excessive drooling ▹ Enlargement of head ▹ Loss of eyesight

6 “By the child’s 3rd birthday, if he’s still alive, his skin will turn yellow and hands pudgy. Most likely he’ll die before he is 4 years old.”

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1 in 400,000 Births around the world

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1 in 3,600 Births among descendants of Eastern European Jews (Ashkenazim)

WHY IS TAY-SACHS DISEASE MOST COMMON AMONG ASHKENAZIM PEOPLE?

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HISTORY

2000 years ago

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Due to violence Peacefully Settled in ● Mediterranean ● and lands ● Yemen ● India

Lived in virtually confined towns Crowded ghettos

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From Israel Jews spread

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Persecution drove Jews out of Western Europe

Spanish Jews (Sephardim) -> lands around Mediterranean and German Jews (Ashkenazim) -> East to Poland -> Lithuanian and Western Russia

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HISTORY End of 19th Century

Lowest TB deaths among Ashkenazic parents of Tay-Sachs children

Waves of murderous anti-Semitic attacks drove millions of Jews out of Eastern Europe -> US most

1972

Present

13 million Jews today - 3/4ths are Ashkenazim (descendants of Eastern European Jews - most risks of Tay-Sachs)

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4 Hypotheses

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1st Hypothesis Mutation as fast as existing copies disappear ▹ New copies of the gene arises as fast as the existing copies disappear with the death of the affected individual ▹ Implies mutation rate of at least 1 per 36,000 births

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1st Hypothesis Why not? ▹ 1 in 3,600 is a frequency far above any human gene ▹ No precedent for one particular gene to mutate much more often in one ethnic population compared to others

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2nd Hypothesis Acquiring the Tay-Sachs gene from others who already had the gene at high frequency According to Arthur Koestler’s “The Thirteenth Tribe”, Ashkenazim are ▹ Not Semitic people ▹ Descendants of Khazar--a Turkic tribe who converted to Judaism

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2nd Hypothesis Why not? ▹ No good evidence to . ▹ Doesn’t explain why it wasn’t eliminated after 1,200 years ▹ Doesn’t explain how the Khazar had it in the first place

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3rd Hypothesis The founder effect and genetic drift ▹ Applicable for small population ▹ New copies of the gene arising fast due to genetic accidents

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Couples in a new island

1 in 1,000,000 Frequency of having a rare gene

1 in 200

Frequency of having the rare gene in a the new population

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100

in a new island

1 Man with the rare gene has lots of kids

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Men has few or no child at all

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98 / 333

Has the Tay-Sachs gene

333 from 1 Couple who migrated to US and had

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Children

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3rd Hypothesis Why not? ▹ Ashkenazim may have been a quite large population ▹ Ashkenazim communities are widespread; the drift will be inconsistent ▹ Natural selection had thousands of years to restore the gene frequency to normal

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Molecular Biologists VS Genetic Accidents Along the stretch of the affected DNA, several different sites of mutation have been identified and 2 of them occur more for non Ashkenazim ▹ It is very unlikely to pump up the frequency of the same gene twice the population

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Molecular Biologists VS Genetic Accidents Tay-Sachs is one of the 10 genetic diseases of Ashkenazim people ▹ Gaucher’s, and Niemann disease also result from accumulation of 2 other fatty substance and defects in 2 other enzymes similar to HEXA

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4th Hypothesis The Tay-Sachs gene is both a curse and a blessing ▹ Tay-Sachs, Gaucher’s, and Niemman, kill individuals who have 2 copies of the faulty gene but help people who only have 1 Ex: Sickle cell (Africa) VS Malaria

Natural selection doesn’t eliminate the gene because there are more Heterozygous individuals who will survive compared to Homozygous ones

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”

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1 / 306 Of grandparents with TS gene died from TB

20% Of the causes of all deaths was TB

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4th Hypothesis Where is the Blessing? ▹ The Tay-Sachs gene was 9-10% more frequent in Austria, Hungary and Czechoslovakia compared to Jews from Poland, Russia, and ▹ Austrians and Hungarian Jews were overrepresented in the 1904 TB report on patients born in Europe between 1860-1900

Where the TB is the biggest threat, natural selection produces the biggest response

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WHY IS THE GENE COMMON JUST IN ASHKENAZIM AND NOT IN NON-JEWS EXPOSED TO TB?

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PREVALENCE OF THE TS GENE IN ASHKENAZIM ▹ Eastern European Jews were businessmen ▹ They were forced to live in the crowded ghettos where TB thrived ▹ High death rate = Higher emigration rate ▹ Jews do not emigrate and were always in the ghettos because of their business

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CONCLUSION ➢ TB resistance is the only plausible hypothesis yet proposed ➢ Evidences are still speculative for the 4th hypothesis ➢ Tay-Sachs disease is both a product of Natural selection and Historical events

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THANKS! Any questions?