Memorial Symposium

Biomedicum Lecture Hall 1 Monday, May 31 at 9-11 am

Special tribute to Academician of Science Leena Peltonen From Individuals to Populations – now and then

ANTTI SAJANTILA, MD, PhD, professor Hjelt Institute Department of Forensic Medicine University of Helsinki ContentContent

 Genetics and identification of individuals

 Identification of Populations

 Studies of Past Populations ContentContent

 Genetics and identification of individuals

 Identification of Populations

 Studies of Past Populations

Early days of forensic genetics - serology

 1901: Karl Landsteiner discovered the human blood groups AB0 (and Rh in 1940)

 1925: "secretor" status described – 80% have blood group substances in their body fluids

 1932: Leon Lattes finds method for AB0 typing of dried blood flakes

 1950's: electrophoresis of serum proteins Revolution in forensic DNA analysis

Nature 314:67-73 (1985) The „Gold Rush“ ~1986-89

 Commercialisation of forensic DNA analysis: - new opportunities for professional services - lack of standards, quality control and assurance - premature introduction into casework

… and the downfall

 Castro Case (New York, 1989) - Admissibility of DNA challenged in pretrial hearings - Evidence to prove presence of the suspect's DNA was dismissed due to lack of standards and biased interpretation Experts vs Experts ~1990-95

 Differences within population may be greater that between populations due to subgroups not conforming to Hardy-Weinberg equilibrium (Lewontin & Hartl, Science 1991)

 1992: National Research Council (NRC) Report I: - accreditation and proficiency testing is essential - "ceiling principle": use the highest frequency of a given allele in any of at least three major racial groups or 10% - collect population data on as many subgroups as possible Science prevails ~ 1996…

 Transition from VNTR to STR systems - Replacing continuous with discrete allele designations

 More population data collected

 1996: NRC Report II - Ceiling principle too conservative - Product rule accepted - Use  to correct for substructure effects

 Introduction of DNA databases in Europe Maturation from science to court

 Societal need and pressure

 Legal system

 Technical

 Scientific

An excellent example of a finding in basic science leading to practice Development of markers and technology

Southern – hybridisation STRs - autosomal -Y-chr

PCR Seq - mtDNA

SNPs - autosomal -Y-chr

mtdna Technical development and marker systems

In 1996 Analysis of 3 Y STRs in 246 individuals in 7 populations

In 2008 Analysis of 500.000 SNPs in 2514 individuals in 23 populations Commentary

Nature 371, 735-738 (27 October 1994) | doi:10.1038/371735a0

DNA fingerprinting dispute laid to rest

Eric S. Lander & Bruce Budowle

Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA and the Department of Biology, MIT, Cambridge, Massachusetts 02139, USA.

Forensic Science Research and Training Center, FBI Laboratory, FBI Academy, Quantico, Virginia 22135, USA.

Abstract

Two principals in the once-raging debate over forensic DNA typing conclude that the scientific issues have all been resolved. IndentificationIndentification ofof IndividualsIndividuals

-- expanding interests Forensic Sci Int. 1992 Sep;56(1):65-76. Identification of the skeletal remains of Josef Mengele by DNA analysis. Jeffreys AJ, Allen MJ, Hagelberg E, Sonnberg A. Department of Genetics, University of Leicester, UK.

J Forensic Sci. 2001 Jan;46(1):173-6. Mitochondrial DNA analysis of the presumptive remains of Jesse James. Stone AC, Starrs JE, Stoneking M. Department of Anthropology, Pennsylvania State University, University Park, USA. O.J Simpson

Did president Jeffersson have an illegitimate child with his slave Sally Hemmings? Foster et al. 1998, Nature

The blue coat of Monica Lewinsky

President Clinton?

COURTESY DR. BRUCE BUDOWLE

IndentificationIndentification ofof IndividualsIndividuals

-- Finland Finland – homicides analysed via PCR 3’ apolipoprotein B gene VNTR

Vuorio et al. 1990 Homicide I Homicide II

controls victim victim Stain 1 Stain 2 Stain 1 Stain 2 Stain 1 Stain 2 Stain 1 Stain 2 Suspect 1 Suspect 1 Suspect 2 Suspect 1 Suspect 1 Suspect 2 Suspect 2 Suspect 2

Leena Palotie Chrisse Syvänen Christian Enholm Australia 1992

Canada 1993

Kenya 1996 ContentContent

 Genetics and identification of individuals

 Identification of Populations

 Studies of Past Populations Population genetic studies - Finland

 Blood group antigens

 Streng 1935, Mustakallio 1989, Nevanlinna 1972

 European affinities, local isolation  mtDNA:

 1994 onwards Sajantila, Lahermo, Majamaa etc.

 European affinities, rel. high diversity, homogeneous  Y-chromosome (STRs, SNPs)

 1996 onwards Sajantila, Kittles, Lahermo etc.

 Eastern component, reduced diversity, regional differences  Autosomal SNPs

 c. 2007 onwards Peltonen, Lahermo, Kayser etc.

 Genetic outlier, significant (but small) regional diff. 2457 samples 309790 SNPs Bottleneck vs. Founder effect (event)

From Jobling, Hurles, Tyler-Smith, Hum.Evol.Genet. Bottleneck vs. Founder effect (event) Archaeologists: continuity theory - Finland colonized c. 11 kya - c. 9.5 kya signs of humans in all parts of Finland - Comb-ceramic invasion c. 7 kya - Corded-ware invasion c. 4 kya

W-Finland

E-Finland

N-Finland

Population density estimated from archaeological finds (M. Tallavaara & P. Pesonen)Is this the case? Slide kindly provided by J. Palo Y chromosome diversity in Finland Y chromosome diversity in Finland

 Great regional differences in pairwise comparison among provinces (Fst-based)  Hierarchical structuring (groups which are homogenous in Y chr)

KY OU MI NC KU CF UU HA VA LA TU LMO

0.001 Y chromosome diversity in Finland

Finns and the other Europeans:

Fin-internalINTERIOR

Fin-East SOUTHEAST

Fin-WestCOAST

Estonia

Vasterbotten

Aland FIN_East – FIN_West ST = 0.113 Norway Slavs – Sweden  = 0.089 Sweden ST

HollDen

NEGermany

Baltic

EasternEurope

Somali

0.02 Y chromosome diversity in Finland

East-West differences in various haplogroups

Lappalainen et al. 2006 Gene 376: 207-215 Y chromosome vs other markers

Interregional differentiation: FST range

 The Y-chromosomal differentiation is conciderably higher!

Slide kindly provided by Jukka Palo Y chromosome vs other markers

Slide kindly provided by Jukka Palo ””InterpretationInterpretation ofof thethe resultsresults - forensic population genetics

 Population structure has to been known  Regional haplotype frequencies have to be estimated

15% 29% 1% ContentContent

 Genetics and identification of individuals

 Identification of Populations

 Studies of Past Populations Forensic ~ AncienDNA ()

Concept ~ Interpretation of the past Reconstruction Method ~ Bio-computing

Neandertals ”Iceman” Paternity testing Birth “Out of Africa” Neolithic expansion Historical persons Extinct animals

500 000 yrs 200 000 yrs 40 000 yrs 10 000 yrs 5 000 yrs 9 months

PAST Ancient DNA Population sampling PRESENT Ancient-DNA - milestones

 Higuchi et al., Nature 1984: DNA Extinct animals sequences from the Quagga, an extinct member of the horse family

 Pääbo et al., Nature 1985: of ancient Egyptian mummy DNA

 Handt et al., Science 1994:Molecular Genetic Analyses of the Tyrolean Ice Man

 Parr et al., Am J Phys Anthropol 1996: Ancient DNA analysis of Freemont Amerindians of the Great Salt Lake wetlands

 Krings et al., Cell 1997: Neandertal DNA sequences and the origin of modern humans Nature Reviews Genetics 2; 353-359 (2001); doi:10.1038/35072071 ANCIENT DNA  2000 onwards acclerated publications of aDNA work with various quality and scientific interest Ancient-DNA – technical challenges

Tyrolean Ice Man Neanertal type specimen Handt et al., Science 1994 Krings et al., Cell 1997 20 000 yrs old ground sloth coprolite CombinationCombination Contemporary population genetics Genealogy – ”Identification” of families Generation Johan Vilhelm Olof Jönsson ~1630 I

Hans II Johan III

Peter Gerhard Samuel IV

Linien I-VII V

VI

VII

VIII

IX

X

XI

Family Snellman Genetic lineage in Finland Snellman Y chromosome halpotype

1600

2000 ??? Switzerland Finland Finnish population revisited (once more) - sampling – genealogy – aDNA

Contemporary ~ 1600 AD ~10000 -1000 BP

aDNA neal. p Ge Contem Isolated populations – any use in genetics?

Slide kindly provided by Jukka Palo Forensic Anthropology and Paternity testing (AD.1961) Memorial Symposium Biomedicum Lecture Hall 1 Monday, May 31 at 9-11 am

Special tribute to Academician of Science Leena Peltonen