Transcript “Unique” Genetic Populations - South Dakota Perinatal Association

“Unique” Genetic Populations
– Get my “Drift”?
Kristen De Berg, MS,CGC
“Unique”
• 87% of SD has Caucasian heritage
• Discuss different populations within SD and in
nearby areas
– Need to think about Genetic, common disease,
and communication
• End with “Unique” genetic populations
Population Genetics
Population genetics is a field of biology that studies the genetic composition of
biological populations, and the changes in genetic composition that result
from the operation of various factors, including natural selection.
Cited in Stanford Encyclopedia of Philosophy Sept. 2006
Population genetics is the study of the distribution of genes in populations and of
how the frequencies of genes and genotypes are maintained or changed.
Cited from Genetics in Medicine, Sixth Edition
Population Genetics
• Some genetic disorders are more likely to occur among
people who trace their ancestry to a particular
geographic area.
• People in an ethnic group often share certain versions
of their genes, which have been passed down from
common ancestors.
• If one of these shared genes contains a disease-causing
mutation, a particular genetic disorder may be more
frequently seen in the group.
Population Genetics
Autosomal Recessive
Mutation in the Instructions
Not this kind of mutant
Mutation in the Instructions
Mutation in the Instructions
Corn Palace
Thorn Palace
Genetic Drift
Genetic Drift or Bottlenecking
Genetic drift is the term used in population genetics to refer to
the statistical drift over time of gene frequencies in a population
due to random sampling effects in the formation of successive
generations.
UNIQUE POPULATIONS
Hutterite
Hutterites
Hutterites
• The Hutterites are a genetically isolated population living on the
North American prairies since the late 1800s [Hostetler, 1985]
• The population now numbers over 40,000, the majority of whom
are descendants of 89 founders [Nimgaonkar et al., 2000].
• The three original South Dakota colonies have given rise to the
three major subdivisions of Hutterite population structure and
members have remained reproductively isolated from each other
since 1910
Genetic Drift
Bowen Conradi
• 1 in 13 carriers
• Mimics Tri 18
• Most infants pass away by 6
months of age.
Maple Syrup Urine Disease
• MSUD is a disorder in
which the body is unable
to process certain protein
amino acids properly.
• Characterized
– Distinctive sweet odor of
affected infants' urine
– Poor feeding, vomiting,
lethargy, and
developmental delay.
– If untreated, maple syrup
urine disease can lead to
seizures, coma, and death.
Maple Syrup Urine Disease
• Maple syrup urine disease
affects an estimated 1 in
185,000 infants
worldwide.
• The disorder occurs much
more frequently in the
Hutterite population, with
an incidence of about 1 in
380 newborns.
Cystic Fibrosis
• M101K and F508D
common mutation in
Hutterites
https://www.youtube.com/watch?v=l8j20UvDzcY
Boycott et al AJMG 2008. Clinical Genetics and the
Hutterite Population
Native Americans
Native American
Both ancient
and recent
Bottlenecks
http://www.plosone.org/article/info%3Adoi%2
F10.1371%2Fjournal.pone.0013996
Genetic Drift in Native Americans
• 1864 Navajo Long Walk
– Forced to walk 500
miles
– War reduced population
from 25k to 2k adults
http://www.pbs.org/pov/sunkissed/phot
o_gallery_background-xp-navajo-longwalk.php#.U5m_p_k7shU
Genetic Drift
XP (Xeroderma Pigmentosum)
• Rare genetic condition
characterized by an extreme
sensitivity to ultraviolet
(UV) rays from sunlight.
• Most develop multiple skin
cancers during their lifetime
• 30% have progressive
neurological problems
• Navajo-higher incidence of
XP vs general population
https://www.youtube.com/watch?v=u8tvW0Oc0tY
Cystic Fibrosis
• Cystic fibrosis is the
most common recessive
disease in Europeans
– 70% to 80% common
mutation ▵F508(F508D)
– R1162X and G542X two
mutations thought to be
unique in the Pueblo
Indians
African Decent
• Large variation- more than many populations
– Implications for pharmacogenomic studies
– 18.5% share European ancestry (WHO study)
– African origin part has similar backgrounds
• At increased risk for
– Asthma, diabetes, lung cancer, stroke, high blood
pressure, and to die of cancer.
Glucose-6-phosphate dehydrogenase
deficiency
Sickle Cell Anemia
The Karen people
• The Karen people
are an ethnic group
living in South-East
Asia.
The Karen people
• Alpha Thalassemia
– Blood disorder that
reduces the production of
hemoglobin
– Hemoglobin carries oxygen
to cells throughout the
body.
– A reduction in the amount
of hemoglobin prevents
enough oxygen from
reaching the body's tissues
www.nhlbi.nih.gov
Ashkenazi Jewish
• Hebrew word “Ashkenaz”
means –Germany
• Most Jewish Americans
are Ashkenazi
• Estimated at 75% of
world Jewish population
• Bottleneck or “random
sampling”-increased risk
for certain conditions
Ashkenazi Jewish
Nature.com
Ashkenazi…
• BRCA1 185delAG, BRCA1 5382insC, and
BRCA2 6174delT-founder BRCA mutations
– 1 in 40 vs 1 in 500 general pop
• Dor Yeshorim carries out anonymous genetic
screening of couples
• 45% of individuals with Jewish ancestry don’t
know it
https://www.youtube.com/watch?v=4bGkUQBw1Rs
Midwest Population
Midwest Population
• Huntington’s Disease
– An inherited disease that
causes the progressive
breakdown of nerve cells in
the brain.
– Disease has a broad impact
on a person's functional
abilities and usually results
in movement, thinking and
psychiatric disorders.
– Triplet repeat disorder
Huntington Disease
•
•
•
•
•
CAH repeat disorder
More than 36 is abnormal
Paternal anticipation
Risk is 50%
This affects family subunit as
much or more as the affected
member
Polycystic Kidney Disease
Polycystic Kidney Disease
Unique Genetic Populations
• 1 in 10 Americans have a rare
disease
– Some common diseases seen in
Adults
• Many adults with a Genetic
disease do not have a primary
provider
• 95% do not have a treatment
or cure
• At our current rate, take
10,000 years to find therapies
for the 7000+ genetic diseases
http://globalgenes.org/who-we-are-2/
Okapi: The Okapi species is closely related to the giraffe
family, not the zebra or even a horse. The Okapi is
native to the Democratic Republic of the Congo in
Central Africa.
References
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Hostetler J. 1985. History and relevance of the Hutterite population for genetic
studies. Am J Med Genet 22:453–462.
Nimgaonkar VL, Fujiwara TM, Dutta M, Wood J, Gentry K, Maendel S, Morgan K,
Eaton J. 2000. Low prevalence of psychoses among the Hutterites, an isolated
religious community. Am J Psychiatry 157:1065–1070.
Flanagan J. et al 2015 A Hutterite condition that mimics Bowen-Conradi syndrome.
S D Med. 2015 Mar;68(3):101-3.
Torbert N. et al. 2015 Bowen-Conradi Syndrome: a trisomy 18-like autosomal
recessive disorder common in Hutterites. S D Med. 2015 Feb;68(2):65-7, 69.
Mroch A. et al 2014 Identification of a founder mutation for maple syrup urine
disease in Hutterites. S D Med. 2014 Apr;67(4):141-3.
Genetics in Medicine, Sixth Edition
Stanford Encyclopedia of Philosophy Sept. 2006
Questions
kennedysdisease.blogspot.com