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------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/master03.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii"
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4/28/2006
 
lGenetic Epidemiology
lTranslational Informatics
l using unique Utah Resources <= /span>
l
l= Lisa Cannon Albright, PhD
l= Genetic Epidemiology
l= Department of Biomedical Informatics
l= University of Utah School of Medicine
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4/28/2006
 
l&= #13;
l&= #13;
= l The Utah Genealogy
l
= l Cancer gene finding in Utah
l
l     Description of = the genetic contribution to health and disease       
l
------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/slide0442.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Familiality of Cancer in Utah
4/28/2006
 
l
l&= #13;
= l The Utah Genealogy = ;
l
= l Cancer gene finding in Utah
l
l     Description of = the genetic contribution to health and disease       
l
------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/slide0351.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Familiality of Cancer in Utah
4/28/2006
History of the Utah Genealogy
l1960’s - Mark Skolnick constructed a compute= rized genealogy of the Parma Valley, Italy from parish records; medical records too diffuse 
<= span style=3D'font-size:63%;visibility:hidden'>l= 3;
l1973 Go= rdon Lark and Luca Cavalli-Sforza discussed how Utah’s genealogical records could strengthen a University cancer center
<= span style=3D'font-size:63%;visibility:hidden'>l= 3;
lMark, Cavalli’s first PhD student, was called in and conceived of a Utah <= /span>genealogy linked to the Utah Tumor Registry=
<= span style=3D'font-size:63%;visibility:hidden'>l= 3;
<= span style=3D'font-size:63%'>lFirst grant  Feb 1975; “Cancer Incidence and Risk Factors by Kinship”
l =
lRGE committee creat= ed as part of a proposal to the Research Resource branch of NIH by an executive order from Governor = Scott Matheson
------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/slide0393.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Familiality of Cancer in Utah
4/28/2006
Original Utah Genealogy Data
= lMormons make up 75% of the state of Utah
<= b>individual Mormons trace their ancestries as far as possible
<= b>records collected in the Family History Library
l
= lThe Utah Genealogy project used 3-generation fa= mily genealogy she= ets submitted by members of the Church of Jesus Chr= ist of Latter-day Sai= nts (early 70’s)
l
= lSkolnick selected sheets containing  > 1 life event in Utah or on the pioneer trail (1840-1850); record linking accomplished during data entry
l<= b>
= lOriginal Utah genealogy included 1.6 million individuals linked in genealogies 6 - 7 generations deep  <= /span>(expanded with = vital records)
l<= b>
= lLinked to Utah cancer registry (death certific= ates, hospital data)
------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/slide0360.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Familiality of Cancer in Utah
    Sample Utah Prostate Pedigree (60 cases)
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Familiality of Cancer in Utah
4/28/2006
 
l
l
l The Utah Genealogy
l
= l Cancer gene finding in Utah <= /span>
l
l     Description of = the genetic contribution to health and disease       
l
------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/slide0379.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Familiality of Cancer in Utah
4/28/2006
 Cancer Genes Localized or Isolated by Genetic Epidemiology and Collaborators using Utah Cancer Pedigrees
l
l
l1987, Science  Neurofibromatosis locus         = ;        
l
l1988, AJHG  Alport Syndrome locus/gene
l
l1994, Nature Genetics=    p16 - Melanoma gene   
l
l1994, Science   BRCA1 gene
l
l1996, Nature Genetics=    BRCA2 gene =
l
l2001, Nature Genetics=   HPC2/ELAC2 prostate cancer gene (?)  
l
l
------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/slide0391.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Familiality of Cancer in Utah
4/28/2006
 
    &nbs= p;
 
l    Why is prostate cancer linkage evidence so difficult to establish and independently confirm? =
l Sex specificity
l Late age onset
l Multiple etiologies, genetic and environmental
l Multiple predisposition genes
l<= /span>
l     Statistical techniques have limited ability to detect linkage in the presence of heterogeneity <= /span>
 
   <= /div>
   &= nbsp; Difficulties with Prostate Cancer Gene Finding 
And ot= hers
------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/slide0445.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Familiality of Cancer in Utah
4/28/2006
 
    &nbs= p;
 
<= span style=3D'mso-special-format:bullet;color:#FF8203;mso-color-index:4;positio= n: absolute;left:-5.28%;top:.3em;font-family:"Monotype Sorts";font-size:75%'>= l Can we identify more genetically homogeneous pedigrees?
1.Select homogeneous cases by cancer characteristics (early diagnosis, aggressive tumor, poor survival, etc)
2.Identify pedigrees with an excess of prostate cancer and other cancers (Cannon-Albright et al, 20= 05a)
3.Limit the number of “founder” chromosomes entering pedigrees- Utah pseudo-isolate populations (Cannon-Albright et al., 2005b)
 
   <= /div>
Prostate Cancer Gene Finding in Utah: 
Reducing Heterogeneity
And ot= hers
------=_NextPart_01C66AC8.3A0BE7A0 Content-Location: file:///C:/CB562974/Lisa_Cannon_Albright_files/slide0413.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Familiality of Cancer in Utah
 Example Irish Isolate Prostate Ped= igree
      (17 prost= ate cases, 9 kidney/bladder  case= s)
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4/28/2006
 
= 3;
We are investiga= ting the power of using high density genotyping (500,000 SNP markers across the genome) in distantly related cases in a single pedigree to identify regions that are shared through inheritance (IBD)
= 3;
The length of any shared region inherited by a set of relatives decreases slowly as the genetic distance betwe= en them increases
= 3;
The probability = under random segregation that there exists any share= d inherited region decreases very quickly---for an extended pedigree any detected sharing is likely to be significant  (Tho= mas et al, submitted)
 
 
 
 
   <= /div>
 The P= ower of Single Utah Pedigrees Familiality of Cancer in Utah
<= span style=3D'mso-spacerun:yes'>        = ;            &n= bsp;    10 cases share 1-2 Mb
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