human genetic variation 2015 fs (1)

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Week of 5/4 - last Discussion, last homework - Discussion sec9on grades will be normalized to class average

Tues 5/5 - Lecture 24 Thurs 5/7 - Lecture 25, SCEQs Tues 5/12 - Exam #4

- we will try to get all your scores up (exams, Discussion, clickers, HW) so you can choose if you want to take the nal

Tues 5/19 - Final Exam (cumula9ve) 1 3 pm here

- exam period is over Weds 5/21 - I will automa9cally drop the lowest score of your 5 exams

Two types of gene therapy in humans Somatic cell gene therapy - introducing a human gene into somatic human cells to help treat a patient with a disease

- legal, has been accomplished but is still experimental - has had major setbacks

Germ line gene therapy - introducing a human gene into the germline of a patient (sperm/eggs) with a genetic disease to cure the disease in the offspring

- not legal in humans, has been done with mice - modifications to the human species genome - proceed with caution

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Lectures 23 and 24

The Human Genome Human Gene1c Varia1on

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19971990

Landmarks in genetics and genomics

1991 1992 1993 1994 1995 1996 1998 1999 2000 2001 2002 2003

20031987 1988 198919851983197719721900 1905 1913 19441865 1953 1966 1974 1982 1984 1986 1990

Gregor Mendel discovers

laws of geneticsRediscovery of Mendels work

Archibald Garrod formulates the concept of human

inborn errors of metabolism

Alfred HenrySturtevant

makes the first linear map of genes

Oswald Avery, Colin MacLeodand Maclyn McCarty demonstrate that DNA

is thehereditary material

James Watson and Francis Crickdescribe the double-helical

structure of DNA

Marshall Nirenberg, Har Gobind Khorana and Robert Holley determine

the genetic code

Stanley Cohen and Herbert Boyer

developrecombinant

DNA technology

Frederick Sanger, Allan Maxam

and Walter Gilbertdevelop DNA-sequencing

methods

First human disease gene for Huntingtons disease is mapped

with DNA markers

First public discussion

of sequencing the human

genomeThe polymerase

chain reaction (PCR) is invented

Muscular-dystrophy gene identified

by positional cloning

First automated DNA-sequencing instrument

developed

International Nucleotide Sequence Database Consortium formed

First-generationhuman geneticmap developed

Development of yeast artificial

chromosome (YAC)cloning

US National Research Council issues report on

Mapping and Sequencing theHuman Genome

Human Genome Organization (HUGO) formed

Cystic-fibrosis gene identified by positional cloning

Sequence-tagged sites (STS) mappingconcept established

GenBank database

established

The Belmont Report on the use of

human subjects in research is issued

G A T C

The Human Genome Project (HGP) launched in the United States

Ethical, legal and social implications (ELSI) programmes

founded at the US National Institutes of Health (NIH)

and Department of Energy (DOE)

First gene forbreast cancer

(BRCA1) mapped

Second-generationhuman genetic map developed

First US genomecentres established

Rapid-data-release guidelines established

by the NIH and DOE

New five-year plan for the HGP in the

United States published

The HGPs human geneticmapping goal achieved

Yeast (Saccharomyces cerevisiae) genome sequenced

First archaeal genome sequenced

First human gene map established

Pilot projects forhuman genome

sequencing begin in the United States

Bermuda principles for rapid and open data release established

The HGPs mouse genetic mapping goal achieved

Escherichia coli genome sequenced

Genoscope (French National Genome

Sequencing Center) foundednear Paris

Roundworm (Caenorhabditis elegans) genome sequenced

RIKEN Genomic Sciences Center established in Japan

New five-year plan for the HGP in the United States published

Single-nucleotide polymorphism (SNP) initiative begins

Chinese National Human Genome Centers established in Beijing and Shanghai

Incorporation of 30,000genes into human genome map

Full-scale human genome sequencing begins

Sequence of first humanchromosome

(chromosome 22) completed

Executive order bans genetic discrimination in US federal workplace

US President Bill Clinton and UK Prime Minister Tony Blair

support free access to genome information

Fruitfly (Drosophila melanogaster) genome sequenced

Draft version of human genome

sequence completed

Draft version of human genome sequence published

10,000 full-length human cDNAs sequenced

Draft version of mouse genomesequence completed and published

Draft version of rat genome sequence completed

Draft version of rice genome sequence completed and published

Finished version of

human genome sequence

completed

The HGP ends with all goals achieved

US Equal Employment Opportunity Commission

issues policy on genetic discrimination

in the workplace

The HGPs human physicalmapping goal achieved

First bacterial genome(Haemophilus influenzae) sequenced

The DOE forms the Joint Genome Institute

US National Center for Human Genome Research becomes the National Human Genome Research

Institute (NHGRI)

To be continued...

The Sanger Centre founded near Cambridge, UK,

(later renamed the WellcomeTrust Sanger Institute)

Mustard cress (Arabidopsis thaliana)genome sequenced

GTGCTGTCCT

Mammalian Gene Collection

M G C

STS Markers

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CUCAGUCAGUCAGUCAG

A GPheLeu

Leu

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HisGln

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Pro

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New strands

Desiredfragmentstrands

3'5'

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DESIGN BY DARRYL LEJAPEAS COURTESY J. BLAMIRE, CITY UNIV. NEW YORK; WATSON & CRICK COURTESY A. BARRINGTON BROWN/SPL; SCIENCE COVERS COURTESY AAAS

HumanGenomeProject

Genetic Map

Physical Map

Cytogenetic Map

25 50 75 100 125 150 Mb

cM2520303020

GATCTGCTATACTACCGCATTATTCCG

Sequence MapClone-Based STS Map

RH Map

2003 Nature Publishing Group

Whole Genome Sequencing

bacteria (1995)

yeast (1996)

nematode (1998)

fruit fly (2000)

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human (2003)

- determining the sequence of an organisms entire genome

Human Genome Project

launched (1990)

sequencing the human genome

- in 2003, the human genome sequence was released - it was a race between a publicly-funded, interna9onal team based in DC and a private company in Bethesda each chose slightly dierent methods to determine the sequence of all 3 billion bases in the human genome

- it relied on years of data from working with model organisms - the two teams 9ed, and reached the nish line at the same 9me

- how was this done?

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Celera and Craig Venter vs.

the public Human Genome Project

The Genome War by James Shreeve (2004)

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whole genome shotgun sequencing

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Cloning DNA fragments into a plasmid

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- digest the en9re human genome (3 x 109 bp) into random small DNA fragments (about 2000 bp each)

- clone millions of human genome fragments into bacterial plasmids and transform each of them into bacteria

- this is a human genome library

- each plasmid in the library contains one small piece of the human genome

- we dont know their DNA sequence - we dont know how the pieces went together originally!

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making a library of human genomic DNA

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- Fred Sanger (Bri9sh) is only one of two people to win the Nobel Prize twice in the same eld and one of only four people to win two Nobel prizes

- Nobel Prize in Chemistry in 1958 for determining the sequence of human insulin and showing proteins have dened sequences and structures

- Nobel prize in Chemistry in 1980 with Walter Gilbert for determining methods to sequence DNA

dideoxy or Sanger DNA sequencing

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- lacks the 3 OH needed to add the next nucleo9de

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- for sequencing by machine, we use uorescently tagged dideoxy versions of the four bases (all in one tube)

- ddATP, ddCTP, ddGTP, ddTTP

- each polymerase stops at a random place along the chain it is making, leaving a uorescent tag on the last base it added

G

G

T

A

T

T

G

A

C

G

G

T

T

T

G

A

C

G

G

T

T

G

A

C

G

G

T

G

A

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G

G

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HEX

HEX

NED

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ROX

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- we can run these DNA fragments through a capillary tube and they are separated them by size (smallest rst)

- we use a laser to iden9fy the color of the tag on each fragment as it comes out the bodom

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- we can run these DNA fragments through a capillary tube and they are separated them by size (smallest rst)

- we use a laser to iden9fy the color of the tag on each fragment as it comes out the bodom

- reading this data on tag colors gives us the sequence of the DNA strand that was made

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assembling the genome sequence

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- the sequence of the ends of all the small fragments is fed into a computer and a computer algorithm determine which pieces overlap, and then assembles them into larger and larger virtual overlapping fragments called con9gs

- any gaps between con9gs are lled in manually

- the resul9ng assembled sequence is the whole genome sequence of the organism

shotgun sequence vs clone by clone sequencing

Craig Venter

Francis Collins

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Animation

Whole-Genome Shotgun

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What did we learn from the human genome sequence?

- almost half of our DNA is relics of ancient transposable elements and viruses, and may not do much

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- how did they identify all the genes? - computer algorithms were trained to identify start codons, stop codons, open reading frames and sites for RNA splicing and to predict genes

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GENBANK site at NCBI holds all the DNA sequence data

GENBANK site at NCBI holds all the DNA sequence data

Gene9c Sequence Data Bank Feb 2014 157,943,793,171 bases from 171,123,749 reported sequences

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BLAST site at NCBI Basic Local Alignment Search Tool - searches your DNA sequence of interest against all known sequences

BLAST site at NCBI Basic Local Alignment Search Tool - searches your DNA sequence of interest against all known sequences - builds on what is already known to identify your gene and what it might encode

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broad categories of of human proteins - largest categories - most genes encode proteins of unknown func9on


- we can now compare the human genome to the genomes of other species that have been sequenced, and ask what makes us the same or dierent from other species

Percentage of DNA in human in common with: Neanderthal 99% last common ancestor 400,000 years ago chimpanzee 96% last common ancestor 7-13 million years ago cat 90% cow 80% mouse 75% last common ancestor 75 million years ago fruit y 60% last common ancestor 600 million years ago nematode worm 50% banana 50% last common ancestor 1.5 billion years ago

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the human genome, now

- it took 13 years to sequence the first human genome (2003) using methods developed in the late 1970s, and cost $3 billion - what have we been doing since then? 1) there has been a worldwide effort to determine more human DNA sequences, and from different ethnic groups, and to find out how much genetic diversity, and what kind, exists in the human population - 2007 - the personal genomes of Jim Watson and Craig Venter were sequenced - 2008 - genomes of anonymous Han Chinese and Nigerian were sequenced

- the Thousand Genome project - the HapMap project (haplotype mapping)

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the human genome, now

- it took 13 years to sequence the first human genome (2003) using methods developed in the late 1970s, and cost $3 billion - what have we been doing since then? 2) there has been a worldwide effort to determine which human genetic variants are associated with human diseases, conditions, and phenotypes - GWAS genome-wide association studies

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1) how can we determine if a given person (or animal, or plant or

any kind of cell) carries a particular DNA polymorphism?

2) what can we do with information about the genetic variation in

a specific individual?

3) what can we learn with information about the genetic variation

in our species?

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human gene9c varia9on

1) how can we determine if a given person (or animal, or plant or any kind of cell) carries a particular polymorphism in their DNA?

a) restriction enzyme digestion of the genomic DNA

b) polymerase chain reaction (PCR) analysis of the genomic DNA c) direct DNA sequencing of the persons genomic DNA d) SNP analysis on the genomic DNA with microarrays

Techniques for iden9fying DNA polymorphisms

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Restriction Fragment Length Polymorphism - RFLP

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SNP identification by RFLP analysis

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an RFLP in the beta-globin gene in sickle cell anemia

DdeI site CTNAG GANTC

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sickle cell anemia carrier determination by RFLP analysis

can identify carriers for sickle cell disease

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Chapter 10 Animation

Testable Genetic Mutations

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1) how can we determine if a given person (or animal, or plant or any kind of cell) carries a particular polymorphism in their DNA?

a) restriction enzyme digestion of the genomic DNA

b) polymerase chain reaction (PCR) analysis of the genomic DNA c) direct DNA sequencing of the persons genomic DNA d) SNP analysis on the genomic DNA with microarrays

Iden9fying DNA polymorphisms

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- STRs are abundant in the human genome (one every 2 kb) - they are very polymorphic (many alleles in the popula9on)

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simple tandem repeats - STRs

- an STR is a site where a small number of base pairs is repeated

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Polymerase Chain Reaction (PCR)

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Each PCR cycle has 3 steps

a. Mel9ng of DNA (95) b. Primer hybridiza9on

(~50-60) c. DNA synthesis (72)

Polymerase Chain Reaction (PCR)

- a DNA sequence in the genome can be greatly amplied by using PCR - mul9ple rounds of DNA synthesis using two primers that hybridize to the ends of the target DNA. - in each cycle, the amount of target DNA is doubled. - aner 30 cycles, there is a billion-fold increase (230) in the amount of the target DNA. - Kary Mullis invented PCR in 1983, and won the Nobel Prize in 1993

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Simple Tandem Repeat Polymorphism (STRPs)

10 alleles in the popula9on 45

individuals are often heterozygous at an STR locus

can distinguish between two homozygotes and heterozygote

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- current SNP chips can analyze >500,000 SNPs at once 47

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- a persons genomic DNA is randomly broken up into small fragments, and all of the fragments are labeled at one end with a fluorescent molecule

- the labeled genomic fragment are then hybridized with the SNPchip

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- a laser is shined on the chip and the fluorescent pattern is recorded and analyzed by a computer to find which SNP variants are present in the persons DNA

human gene9c varia9on - what can we do with this kind of personal gene9c informa9on

1) mapping human disease genes

2) determining a persons suscep9bility to disease based on their genes

3) forensics

4) understanding human evolu9on

5) understanding migra9on and ancestry

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Identifying disease genes using affected families

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cys$c brosis

Disease genes can be mapped using DNA markers

GWAS - genome-wide association studies

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recent genome-wide association studies (in last 5 years)

- have identified SNPs associated with the many diseases or conditions:

heart disease breast cancer restless leg syndrome (!)` atrial fibrillation glaucoma colon cancer amyotrophic lateral sclerosis type 2 diabetes multiple sclerosis rheumatoid arthritis bipolar disorder slow onset of AIDS

18 SNPs correlated with type 2 diabetes

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Direct To Consumer gene9c tes9ng services

deCODE decodeme.com Navigenics navigenics.com 23andme 23andme.com

For $600 - $2500 and a sample of saliva, they will report back to you your SNP pattern for 500,000 SNPs (out of maybe 4 million) 23andme reports on SNPs for 150 traits/conditions/diseases (for 54 of them, they) give you information about conditions and traits for which there are genetic associations supported by multiple, large, peer-reviewed studies. Those associations must also have a substantial influence on a person's chances of developing the disease or having the trait. Because these associations are widely regarded as reliable, we use them to develop quantitative estimates and definitive explanations of what they mean for you.

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Age-related Macular Degenera1on Alcohol Flush Reac1on Alpha-1 An1trypsin Deciency BRCA Cancer Muta1ons (Selected) BiOer Taste Percep1on Bloom's Syndrome Celiac Disease Crohn's Disease Cys1c Fibrosis (Delta F508 muta1on) Earwax Type Eye Color G6PD Deciency Glycogen Storage Disease Type 1a Hemochromatosis Lactose Intolerance Malaria Resistance (Duy An1gen) Muscle Performance Non-ABO Blood Groups Norovirus Resistance Parkinson's Disease Prostate Cancer Psoriasis Resistance to HIV/AIDS Rheumatoid Arthri1s Sickle Cell Anemia & Malaria Resistance Type 1 Diabetes Type 2 Diabetes Venous Thromboembolism

Abdominal Aor1c Aneurysm Alcohol Dependence Ankylosing Spondyli1s An1depressant Response Asthma Atrial Fibrilla1on AOen1on-Decit Hyperac1vity Disorder Avoidance of Errors Back Pain Baldness Beta-Blocker Response Bipolar Disorder Birth Weight Bladder Cancer Blood Glucose Brain Aneurysm Breast Cancer Breast Cancer Risk Modiers Breas`eeding and IQ C-reac1ve Protein Level Caeine Metabolism Celiac Disease: Preliminary Research Chronic Lymphocy1c Leukemia Clec Lip and Clec Palate Cluster Headaches Colorectal Cancer Creutzfeldt-Jakob Disease Developmental Dyslexia Endometriosis Esophageal Cancer Eye Color Food Preference Freckling Gallstones

Gesta1onal Diabetes Glaucoma Gout HDL Cholesterol Level HIV Progression Hair Color Hair Thickness Heart AOack Height Heroin Addic1on High Blood Pressure (Hypertension) Intrahepa1c Cholestasis of Pregnancy Kidney Disease Larynx Cancer Longevity Lou Gehrig's Disease (ALS) Lung Cancer Lupus (Systemic Lupus Erythematosus) Male Infer1lity Measures of Intelligence Memory Mul1ple Sclerosis Neuroblastoma Nico1ne Dependence Obesity Obesity: Preliminary Research Obsessive-Compulsive Disorder Odor Detec1on Oral and Throat Cancer Osteoarthri1s Pain Sensi1vity Parkinson's Disease: Preliminary Research Peripheral Arterial Disease Persistent Fetal Hemoglobin Placental Abrup1on Preeclampsia 57

My Beau9ful Genome Lone Frank 2011

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Pharmacogenomics

- iden9fying SNPs that correlate with beder or worse responses to certain drugs will allow beder prescribing by physicians

- example - codeine is converted to morphine in the liver by the enzyme cytochrome P450 CYP2D6 - 10% of people have a muta9on that abolishes enzyme func9on - codeine is of no benet to these people

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Human gene9c varia9on: forensics

- the FBI uses a set of 13 STRs to genotype individuals and crime scene samples

- they know the number and frequency of the alleles at these 13 sites in Caucasian, African-American, Hispanic and Asian populations in the US

- obtain crime scene sample - semen, blood, hair cell, skin cells

- do PCR on each of the 13 loci from the sample and suspects

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- at one of the real sites used, people have between 5 and 16 repeats of GATA - so 12 alleles and 78 genotypes (homozygous and heterozygous) 62

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example - imagine a person matches a semen sample at 13/13 loci, - what is the chance that he is innocent and this is random bad luck?

- how often would that pattern arise by chance?

- if 13 alleles are present at 50% frequency in population = 0.5013= 1/8,192

- if 13 alleles are present at 10% frequency in population = 0.1013 = 1/10,000,000,000,000 (1 in 1013)

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WA

15, 16 18, 19

15, 16

FGA

23, 27 21, 23

23, 27

3S1358

15, 17 17, 17

15, 17

3S1358

15, 17 17, 17

15, 17

D21S11

28, 30 27, 30.2

28, 30

D18S51

12, 18 14, 18

12, 18

D5S818

13, 13 9, 12

13, 13

D13S317

12, 12 12, 12

12, 12

D7S820

10, 11 9, 10

10, 11

CSF1PO

8, 11 11, 12

8, 11

TPOX

7, 8 8, 8

7, 8

THO1

9.3, 9.3 6, 9.3

9.3, 9.3

D16S539

9, 13 11, 12

9, 13

SSR Crime sample Suspect A Suspect B

Frequency of Suspect 0.13 0.22 0.31 0.34 0.06 0.11 0.29 0.21 0.26 0.18 0.30 0.38 0.10 Bs genotype

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- CODIS - FBIs database - Combined DNA Index System

- as of February 2007 it had data from 67,000 crime scenes and 1.5 million individuals convicted of felonies or arrested for felonies (more recently) - CODIS has made more than 45,000 hits

- first case and Snowball case

Abraham Lincolns DNA by Philip Reilly (2000) The Strongest Boy in the World by Philip Reilly (2006) Tears of the Cheetah by Stephen OBrien (2003) When a Gene Makes YouSmell Like a Fish by Lisa Seachrist Chiu (2006)

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Human gene9c varia9on: paternity

- similar types of analyses are used in paternity cases

- analysis for one SSR shown

- A = accused males DNA - C = childs DNA - M = mothers DNA - A=C = mixture of A and C

case 1 case 2

A A + C

C M A A + C

C M

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Human gene9c varia9on: forensics - can also do this to identify body remains

- 911 victims - Russian Romanov family (last czar)

- in this case, you use DNA from relatives as the match

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Human gene9c varia9on: human evolu9on

- following human evolution, migration and history via: - changes in mitochondrial DNA sequence

- changes in human Y chromosome sequence

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human evolu9on and mitochondrial DNA

- mitochondria (and chloroplasts) are self-replica9ng organelles that contain their own DNA - supercoiled circles of DNA

- mammalian mtDNA is only 16,500 bp (16.5 kb)

- about 40 genes encode proteins used in mitochondria, such as the DNA polymerase for replica9ng mtDNA and a few proteins used in respira9on

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- human eggs and sperm both contain mitochondria

- aner fer9liza9on, when the sperm and egg fuse, the mitochondria from the sperm are destroyed, so that all the mitochondria in the ospring are inherited from the mother

- so genes in the mitochondrial DNA show non-Mendelian inheritance paderns - uniparental inheritance - also called extranuclear inheritance or cytoplasmic inheritance

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- so human mitochondrial DNA - is passed only through the maternal side - does not undergo recombina9on

- therefore, in the absence of new muta9ons, your mitochondrial DNA is exactly the same as your mothers, grandmothers, etc

- if you went back six genera9ons in your own family tree, you'd see that your nuclear DNA is inherited from 32 men and 32 women

- your mtDNA, on the other hand, would have come from only one of those 32 women, on your mothers side.

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- so human mitochondrial DNA - is passed only through the maternal side - does not undergo recombina9on

- therefore, in the absence of new muta9ons, your mitochondrial DNA is exactly the same as your mothers, grandmothers, etc

- if you went back six genera9ons in your own family tree, you'd see that your nuclear DNA is inherited from 32 men and 32 women

- your mtDNA, on the other hand, would have come from only one of those 32 women, on your mothers side

- but there is muta9on in mtDNA, from errors during DNA replica9on and from environmental causes

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- star9ng with all the dierent types of mitochondrial DNA variants present around the world today, we can work backwards to nd a most recent common ancestor (MRCA)

- the mtDNA molecule that was mutated to give rise to all exis9ng mtDNA molecules around today

- by applying a molecular clock (1 change/3800 years) we can es9mate how long ago she lived

- the last female common ancestor of all people currently on the planet - named Mitochondrial Eve

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1987 - results from analysis of human mtDNA varia9on showed:

- there is twice as much mitochondrial diversity in Africa as in all the rest of the world (true for nuclear genes too - there is more diversity in Africa than all the rest of the world combined)

- 3 of 4 major mitochondrial lineages are found only in Africa,

- 1 mitochondrial lineage is found outside of Africa and it shares a most recent common ancestor with African lineages about 50,000 YA

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Figure 17.31: Phylogenetic tree of human mitochondrial DNA 77


1987 - results from analysis of human mtDNA varia9on showed:

- there is twice as much mitochondrial diversity in Africa as in all the rest of the world, and 3 of 4 major mitochondrial lineages are found only in Africa

- a subset of mitochondrial muta9ons are found outside of Africa - these share a MRCA with African lineages about 50,000 YA

- believed to be when a small popula9on of humans (5,000?) migrated out of Africa to populate the rest of the world about 50 - 100,000 YA

- supports the Out of Africa hypothesis put forward by paleontologists

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Figure 17.32: The dispersal of modern human populations

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That's Ridiculous How Could a Single Being Populate a Planet? And this is where the confusion sets in. A single organism can't populate a planet. The evidence didn't suggest a single woman living in isola1on from members of her own species. What it suggested was a gene1c boOleneck a period in human history when the popula1on was so small that the gene1c expressions of a single woman could have an impact on all humans living on the planet today. She didn't live alone she would have lived within a community. She didn't just pump babies out, either. There is no reason to suppose that she had more than one female child. But there is reason to suppose that whatever female children she had, they contained specic advantages for survival over the rest of the popula1on.

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human evolu9on and the Y chromosome

- the human Y chromosome contains the sex-determining gene SRY - which encodes Testis-Determing Factor - tells the developing gonad to develop as a testis

- the Y chromosome only contains small regions at either end that are homologous to the X chromosome (called the pseudoautosomal regions)

- other than this, the Y chromosome has very few genes

- most of the X and Y are not homologous and do not pair during meiosis

- it is assumed that the X and Y chromosomes were once a normal pair of homologous chromosomes, and that over time the Y has lost sequences present on the X chromosome

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- so the Y chromosome is present only in males, and does not go through recombination along most of its length

- therefore mutations that arise in one male will be passed on to that males sons without changing

- there are ~30 simple sequence repeats (SSRs) along the Y chromosome that can be easily mapped

- as was done for females and mtDNA, using the variation in all of the Y chromosomes in the current human population, it was estimated that the last common ancestor of all human males lived 50,000 years ago

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Mapping human history with the Y chromosome

- Genghis Khan - founder of the Mongol Empire in the 13th century - stretched from China to Europe - he and his descendants were very prolific - his son had 40 sons, his grandson Kubilai Khan had 22 - mapping 32 Y chromosome markers from >2000 Asian men showed a common pattern - the most recent common ancestor of all the men with this pattern lived ~1000 years ago - assumed to be Genghis Khan

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- the Lemba are a Bantu-speaking tribe living in S. Africa and Zimbabwe

- they practice male circumcision, have dietary restrictions similar to those of Jewish people, and have an oral history that says their ancestors arrived by boat from N. Africa/Middle East

- mapping 12 Y chromosome markers in 136 Lemba men showed they have two common patterns of variation - one is similar to the Bantu pattern - the other is similar to the Cohanim pattern of Jewish people - the last common ancestor of these men lived 3,000-5,000 years ago, around the time that the Jews were exiled from Assyria

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- Gypsies - tribe of nomadic people arriving in Europe about 1000 years ago - widely persecuted - called Gypsy because of legend they came from Egypt, but they call themselves Roma - their language is similar to languages spoken on the Indian subcontinent

- 12 million Roma today, in many countries - Y chromosome analysis of men from 14 Roma populations around the world showed 45% of them had a related pattern of variation

- the most closely related haplotype is found on the Indian subcontinent, suggesting this as their site of origin

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gene9cs and human history and migra9on

- dierent groups of people, geographically isolated on the planet, have dierent paderns of DNA changes (haplotypes) for their genomic DNA (SNPs), Y chromosomes and mitochondrial DNA

- therefore, you can tell what part of the planet a persons ancestors came from by examining their DNA and comparing it to samples from living popula9ons on the planet

- gene9c ancestry tes9ng - $100 - $900

- s9ll allowed 2014 deCODE decodeme.com Navigenics navigenics.com 23andme 23andme.com

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human genetic variation 2015 fs (1)

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