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Note: Description: BRACHYDACTYLY with HYPERTENSION - this condition is characterised by stubby fingers, hands and sometimes feet, and this is an hereditary condition.
BRACHYDACTYLY WITH HYPERTENSION
A Hypertension Gene Located by Whole-Genome Scanning
Dr. Herbert Schuster Max Delbr�ck Center for Molecular MedicineGermany
Pedigree for the Turkish family with hereditary hypertension linked tostubby fingers (brachydactyly). Linkage analysis included 25 affectedand 21 unaffected members.
Using the ABI PRISM(TM) Linkage Mapping Set and ABI PRISM(TM) 377 DN ASequencer, Dr. Herbert Schuster's group at the Max Delbr�ck Center forMolecular Medicine in Berlin has localized a gene that is responsiblefor an autosomal dominant form of hypertension.
This feat was accomplished in just two months and demonstrates thepower of the ABI PRISM(TM) genetic analysis systems for whole-genomescans to establish genetic linkage.
A 1973 paper had documented genetic linkage between severehypertension and short, stubby fingers (brachydactyly) in a largeTurkish family. Family members had observed for generations that if achild was born with stubby fingers, he or she would die of a strokebefore reaching 50.
With the encouragement of colleagues Dr. Friedrich Luft and Dr. ThomasWienker, Dr. Schuster decided to reinvestigate this family in anattempt to locate and identify a hypertension gene. Dr. Schuster,Associate Professor of Medicine at the Delbr�ck Center, is a leadingauthority on disorders of lipid metabolism. He has devoted much of hiscareer to studying the genetic risk factors for cardiovascular disease(CVD ). The hypertension project seemed ideal for his newlyconstructed facility equipped with the latest ABI PRISM(TM) systems.
Dr. Schuster and his team journeyed to Turkey to interview familymembers, create a pedigree of affected and unaffected individuals, anddraw blood samples. Back at the laboratory, DNA was extracted andfluorescent labeled PCR primers from the Linkage Mapping Set were usedto amplify microsatellite markers in a whole-genome scan.
PCR was carried out on the ABI CATALYST(TM) Molecular Biology LabStation a pipetting robotics system for genetic analysis applications.Products of up to 18 markers were pooled and electrophoresed in onelane on the 377 DNA Sequencer, and the system's ABI GeneScan softwaresized the fragments while ABI Genotyper automatically scored thealleles .
Dr. Herbert Schuster, with his field genetics team in Turkey. HakanToka and Okan Toka, Turkish students who helped communicate with theTurkish families; Dr. Thomas Wienker, the Delbr�ck geneticist whosuggested reinvestigating the hypertension linkage, Dr. NihatBilganturan, the Turkish pediatrician who first described the linkagein 1973, and Dr. Friedrich Luft, head of the Delbr�ck clinicalresearch unit.
In a scant two months, a team of four established linkage betweenmarkers on chromosome 12 and the hypertension gene. In contrast, ittook an army of researchers 10 years to localize the Huntington'sdisease gene.
Dr. Schuster estimates that the Linkage Mapping Set saved him 3-4years of work by providing an already-made index map covering thewhole genome at an average resolution of 10 cM. The 377 DNA Sequencerprovided additional speed and throughput. Under ideal conditions, thisinstrument permits a user to multiplex an average of 15 markers perlane in 24-36 lanes in 3 runs per day.
"The fluorescence dye technology helps in multiplexing and made itpossible for us to do more tests at the same time. This helped tominimize variability and also reduced costs," Dr. Schuster noted.
Accurate and reliable fragment sizing by the ABI GeneScan software andallele calling by the ABI Genotyper software were also critical tothis success. The use of an internal lane DNA size standard madepossible by PE Applied Biosystems' patented four-color fluorescencetechnology provides unmatched accuracy of sizing by eliminatinglane-to-lane and gel-to-gel variability. "The internal lane standardwas particul arly helpful for comparing data between differentexperiments," Dr. Sc huster said.
Dr. Schuster believes that localization of this hypertension gene maygive scientists a clue to understanding the more common form ofhypertension, which has a complicated mode of inheritance and isstrongly influenced by environmental factors. This research shouldallow the development of: 1) new drugs precisely targeted at genesinvolved in the disease and, 2) screening tests that will identifyat-risk individuals and allow closer monitoring with earlier, and moreeffective, clinical intervention.
Data from the whole genome scan of members of the Turkish family.Primers from Panel 17 (chromosomes 12 and 13) of the ABI PRISM(TM)Linkage Mapping Set were used to amplify allelic markers at ninemicrosatellite loci. Left: Gel view from the ABI PRISM(TM) 377 DNASequencer showing samples from 14 family members, one in each lane.The nine loci are multiplexed on the basis of allele size and threedifferent colors of fluorescent labels (blue, green, and yellow). Thered bands are the internal size standard. Right: Genotyping data forfour different family members. These individuals were typedautomatically at one locus by the ABI Genotyper software. The fourindividuals are typed as (168, 172), (166, 170), (170, 172), and (170,170) on the basis of allele size in base pairs.
Hypercholesterolemia Assay
In a related effort, Dr. Schuster and his coworkers have developed afluorescent oligonucleotide ligation assay (OLA) that detects 19different mutations in two major genes affecting the metabolism oflow-density-lipid (LDL) cholesterol in patients with familialhypercholesterole mia (FH). [3] The assay is a two-step, one-tubereaction that is analyzed automatically on the 377 DNA Sequencer, andis readily adaptable for routine clinical use. The assay will permitidentification of individuals in FH families who are at increased riskof CVD. Hypercholesterolemia, like hypertension, is a risk factor forCVD.
Dr. Schuster looks forward to the day when DNA-based testing for CVDrisk factors will be done routinely in clinical settings. He believesthe flexibility, accuracy, and reliability of the ABI PRISM(TM)instruments, reagents, and software will be crucial to the developmentof such tests.
"The ABI PRISM(TM) system offers great flexibility and high throughput. We can use the same instruments, the same reagents, and the samesoftware for all currently available methods for genetic analysis,including linkage analysis, SSCP, sequencing, and mutation detection."
"Clinical geneticists need all these different applicationssimultaneously sometimes even from the same samples. The ability toprovide all these applications is absolutely unique to the ABI system.There is no other company offering a complete genetic analysissystem."
"And with this single integrated ABI system, we can develop rigorousstandards and quality control, which will be critical to thedevelopment of routine DNA-based clinical tests. The internal lanestandard capability, for instance, will be extremely useful inachieving quality control of these tests."
Once DNA screening is set up as a routine clinical test, it can betransferred from the research lab to a routine DNA diagnostic lab.When this happens, Schuster says he might switch to anotherinstrument, such as the ABI PRISM(TM) 310 Genetic Analyzer acapillary electrophores is system that offers total automation, fromloading the gel and the sample to data analysis.
References
Schuster, H. et al., Nature Genetics 13: 98-100 (1996).
Bilganturan, N. et al., J. Med. Genet. 10: 253-259 (1973).
Baron, H. et al., Nature Biotechnology.
SERVICE RECORD WWll
Name PRICE, JAMES MATTHEW
Service Royal Australian Air Force
Service Number 38875
Date of Birth 17 May 1923
Place of Birth CUE, WA
Date of Enlistment 31 May 1941
Locality on Enlistment BIG BELL
Place of Enlistment PERTH, WA
Next of Kin PRICE, MATTHEW
Date of Discharge 28 Mar 1946
Rank Leading Aircraftman
Posting at Discharge 12 Squadron
Jim Price and family are still living at, and own/manage CoodardyStation, Cue in the Murchison area of Western Australia. A lot ofbooks have already been written about the area and also about CoodardyStation in general. I am sure that if anyone has an interest inknowing more about this large sheep station property and its originsthey will find many book at their local library.
In March 1979, The Price Family of Coodardy Station played host to HisRoyal Highness, The Prince of Wales.
Prince Charles spent three nights and two days at Coodardy Station.(See photos in the Family Album taken at this time.)
James Matthew Price (Jim) MBE. OAM. JP..
Investiture, Government House, Perth WA. Thursday 23 September 1993.(see Photo in Family Album)
To be Awarded The Medal of the Order of Australia in the GeneralDivision:
President, Cue Shire Council since 1971-1996 Chairman, Murchison Ward,Country Shire Councils' Association of WA since 1971-1996Association's Member for WA Agricultural Protection Board from1971-1987, Association's Member for the WA Exotic Diseases Committee(Animal) since 1979.
Represented the Pastoralists' and Graziers' Association on the Boardsince 1987.
Executive Member, number of committees of the Pastoralists' andGraziers' Association of WA since 1952.
Deputy Member, Pastoral Board of WA since 1987.
Member, Department Agriculture's Rangeland Management RegionalResearch Liaison Committee since 1979.
Member Cue District Soil Conservation Committee since 1989.
Has been active with the Cue Bi-Centennial Committee, Keep AustraliaBeautiful Council, Racing Association, Rifle Club and Golf Amongothers.
Life Member Murchison Racing Association.
Life Member East Gascoyne Race Club.
Life Member Cue Rifle Club.
James Matthew Price is the 1st Cousin once removed of Cardinal SirNorman Gilroy - the First Cardinal of Australia.
A small wooden hand seal with the Arms of the Price Family, is inpossession of (Jim) James Matthew Price. This seal has been handeddown through each generation of the descendants possibly as far backas Matthew Guerin Price.
There is mention of a similar seal in the story of earlier ancestorsin the Price family when Thomas Price originally arrived in theChannel Islands from his ancestoral home in Wales. It is hard toestablish a date of manufacture or if there is a connection to thistime or the possibility that it was made for Matthew Guerin Price, totake to Naples Italy in about 1815/16.
Since 1968, when an aeroplane was purchased at Coodardy, aerialmustering for the shearing with several motorbikes on the ground cutthe time required from 3 weeks to 3 days. Jim renewed his love offlight which began towards the end of WW2, with aerial musteringand his many commitments on committees and boards around the State andat 77 Jim is still flying.
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