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PGA 1: Männlich, etwa 50 Jahre alt

Diese Seite enthält die Ergebnisse der persönlichen Genomsequenzierung. Außerdem können die TeilnehmerInnen freiwillig weitere Informationen zu ihrer Person veröffentlichen, zum Beispiel zu körperlichen Eigenschaften, Röntgenbilder oder Auszüge aus ihrer Krankenakte.

Auf ausdrücklichen Wunsch von PGA 1, veröffentlichen wir hier den Namen des ersten freiwilligen Teilnehmers von Genom Austria: Giulio Superti-Furga

Genomvisualisierung PGA1: Normale Variabilität

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Die obige Darstellung zeigt alle Positionen, in denen sich das jeweilige persönliche Genom vom menschlichen Referenzgenom unterscheidet, und sie zoomt anschließend beispielhaft auf eine dieser genetischen Variationen.

Genetische Herkunft: Europäisch

Die folgende Darstellung ordnet jedem Teilnehmer und jeder Teilnehmerin eine genetische Herkunft zu, basierend auf dem Vergleich mit anderen Personen mit bekannter Herkunft.

Karte der genographischen Herkunft als PDF anschauen

Genom online anschauen

Genom-Browser dienen dazu, einzelne Bereiche im Genom mit den dazugehörigen Annotationen wie zum Beispiel Genen anzuschauen. Ein verbreitetes Werkzeug ist der UCSC Genom-Browser, der von der University of California Santa Cruz (UCSC) entwickelt wurde. Um die Genom-Daten direkt im UCSC Genom-Browser aufzurufen, verwenden sie bitte diesen Link:

UCSC Genome Browser Hub laden

Annotation: Häufige genetische Varianten

Für häufige genetische Varianten besteht die Möglichkeit, sie im Kontext anderer Personen mit denselben Varianten auf ihre Assoziation mit klinisch und körperlich relevanten Eigenschaften dieser Personen zu analysieren, wobei die beobachteten Zusammenhänge meist eher schwach sind. Die folgende Webseite enthält eine computerbasierte Annotation von häufigen genetischen Varianten. (Link zum Report)

Annotation: Seltene genetische Varianten

Seltene genetische Varianten sind oft schwierig zu interpretieren, wenn zum Beispiel ein Gen mit einer bekannten Funktion an einer vorher unbekannten Stelle verändert ist. Die folgende Liste enthält eine computerbasierte Annotation von seltenen Varianten (XLSX-Datei bitte herunterladen und in Excel oder einem anderen geeigneten Programm öffnen).

Ausgewählte Ergebnisse

Im Folgenden werden einige konkrete Ergebnisse vorgestellt, die bei der Analyse dieses persönlichen Genoms besonders interessant erschienen. Aufgrund der Vielzahl an genetischen Varianten in jedem persönlichen Genom ist diese Auswahl ein Stück weit willkürlich.

Außerdem ist es wichtig, diese Ergebnisse nicht als „in Stein gemeißelte Wahrheiten“ zu interpretieren, und zwar aus mehreren Gründen: (1) Der Mensch ist sehr komplex, und die meisten Eigenschaften (z.B. Körpergewicht), Verhaltensweisen (z.B. Rauchen) und Krankheiten (z.B. Krebs) ergeben sich aus dem Zusammenspiel von Genen, Umwelteinflüssen und dem Zufall. (2) Die Wissenschaft weiß noch recht wenig darüber, wie man persönliche Genome von gesunden Menschen interpretiert. (3) Die Methoden zur Genomsequenzierung sind relativ neu, und es kann vereinzelt zu technischen Fehlern kommen. Um die Interpretation möglichst transparent zu machen, verweisen wir jeweils auf Quellen mit weiteren Hintergrund-Informationen, aus denen auch die englischsprachigen Zitate entnommen sind.

Potenziell medizinisch nützliche Informationen 
(Achtung: Verwendung für medizinische Zwecke erst nach Validierung durch ein medizinisch-diagnostisches Labor!)

Erhöhte Wirkung von Coumadin/Warfarin-Medikamenten zur Blutverdünnung (daher niedriger zu dosieren):

rs9934438(T:T) -> Coumadin (warfarin) resistance.
rs9934438(C>T) 1173C>T polymorphism in the VKORC1 gene. The T allele frequency was 38.8%. Individuals with the TT genotype who are treated with warfarin may require a lower coumadin/warfarin dose compared to patients with the TC or CC genotype. Other genetic and clinical factors may also influence a patient's required dose of warfarin. Persons with at least one T-allele had a statistically significant 19% (95% CI 2 to 40%) risk increase of calcification of the aortic wall compared to CC homozygous persons.
www.snpedia.com/index.php/Rs9934438
www.ncbi.nlm.nih.gov/clinvar/variation/37344/

Reduzierte Verstoffwechslung von bestimmten Medikamenten (Mephenytoin, Plavix, etc., daher weniger Wirkung und mehr Nebenwirkungen):

rs4244285(G;A)
rs4244285(G>A) is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*2 variant. This variant is the most common reason for poor metabolism of compounds like mephenytoin (an anti-convulsant), some antidepressants, the anti-platelet drug Plavix, and some drugs used for ulcer conditions of various types. In Caucasians, SNPs in CYP2C19 are relatively rare. A study of 1,477 subjects with acute coronary syndromes who were treated with clopidogrel as part of the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38 study concluded that rs4244285(A) allele carriers had a 1.53x increased risk for death from cardiovascular causes, myocardial infarction, or stroke, as compared with noncarriers.
www.snpedia.com/index.php/Rs4244285
https://www.pharmgkb.org/rsid/rs4244285

Häufige genetische Varianten mit geringen statistischen Effekten (diese genetischen Varianten sind in der Bevölkerung weit verbreitet und meist mit geringen Abweichungen vom Durchschnitt verbunden)

Erhöhtes Risiko für Herz-Kreislauf-Erkrankungen:

rs1333049(C;C) & rs10757278(G;G) & rs2383206(G;G)
rs1333049(G>C) has been reported in a large study to be associated with heart disease, in particular, coronary artery disease. The risk allele (oriented to the dbSNP entry) is most likely (C); the odds ratio associated with heterozygotes is 1.47 (CI 1.27-1.70), and for homozygotes, 1.9 (CI 1.61-2.24). This SNP has also been reported to have the highest association of any SNP studied in a subsequent experiment conducted with the resources of the German MI [Myocardial Infarction] Family Study. It has been shown that regularly eating raw vegetables and fruit can reduce the risk to the same level as people without any copies of this SNP. rs10757278(A>G) is one of several clustered together in a region of chromosome 9 that has been linked to increased risk for heart disease and potentially diabetes. The overall estimate of heart disease cases that may involve this SNP is 20-30%. The risk allele, rs10757278(G), shows an increased association for myocardial infarctions ("MI"; heart attacks) both in general and more specifically in so-called early onset MI. The odds ratio for rs10757278(G;G) individuals relative to rs10757278(A:A) "noncarrier" individuals is 1.64 (CI: 1.47-1.82), and for carriers of one risk allele, i.e. rs10757278(A;G) individuals, 1.26. rs2383206(A>G) can significantly increase the risk of heart disease. About one in every four Caucasians are thought to carry the variants, and their risk of coronary heart disease is increased by 30 to 40%. The chromosomal region where these SNPs are located is 9p21, and has no known genes.
http://www.snpedia.com/index.php/Rs1333049
http://www.snpedia.com/index.php/rs10757278
http://www.snpedia.com/index.php/Rs2383206

rs2200733(T;T)
rs2200733(C>T) was found to be associated with atrial fibrillation in a study of European and Asian populations. The odds ratio associated with one or more copies of the risk allele was ~1.5x increased risk of Atrial Fibrillation and ischemic stroke. The risk allele affects the formation of the heart and gives a higher risk of Atrial Fibrillation (quivering of the top part of the heart), and Cardioembolic and Ischemic strokes (blocked blood flow to the brain). Based on several quality studies.
www.snpedia.com/index.php/Rs2200733

rs2943634(C;C)
rs2943634(C>A) is a SNP found to be reproducibly associated with heart disease-> higher risk of ischemic stroke. It is associated with high density lipoprotein (HDL) cholesterol.
www.snpedia.com/index.php/Rs2943634

rs6318(C;-)
rs6318 is a SNP within the serotonin 2C receptor gene located on the X chromosome. Since it is located on the X chromosome, males will be hemizygous and either (C;-) or (G;-), whereas females will either homozygous (C;C) or (G;G) or heterozygous (C;G). In most of the studies heterozyous (C;G) females were roughly statistically equivalent to females carrying the common non-risk (G;G) genotype. (C;-) males or (C;C) females have an 1.4x increased risk for cardiac events; apparently stress (cortisol) related. Possibly, stronger emotional response to stress, and slightly (?) higher risk for affective disorders (major depressive and bipolar disorders). Poorer lipid profiles have also been reported.
www.snpedia.com/index.php/Rs6318

Erhöhtes Risiko für Bluthochdruck:

rs891512(A;G)
rs891512(G>A) is an intronic variant in the NOS3 gene significantly associated with blood pressure. GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (-2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (-1.9 mm Hg; P = 0.018) than A-allele carriers.
www.snpedia.com/index.php/Rs891512

rs10830963(G;G), rs3781638(C;T), rs1801282(C;G)rs17817449(T;G) - Erhöhtes Risiko für Übergewicht, Fettleibigkeit und Diabetes                                    rs10830963(C>G) was significantly associated with higher fasting plasma glucose concentrations and reduced insulin release.                                    

rs3781638(C>T) displayed significant association with lower fasting plasma glucose levels and increased OGTT-induced insulin release. A study totaling 19,000+ Europeans concluded that rs10830963 had the most influence of any gene SNP on the risk for type-2 diabetes.

rs1801282(C>G) is a common SNP in the peroxisome proliferator-activated receptor PPARG gene. The more common (C) allele (in dbSNP orientation) encodes the 'Pro' amino acid at this SNP position. The SNP.has been reported to be associated with metabolic syndrome, but other studies have not been able to replicate any strong or significant effect. Reportedly, the (G) allele increased the risk of isolated impaired fasting glycemia (OR=1.64) but not isolated impaired glucose tolerance.

rs17817449(T>G) is located within the FTO gene and has been associated with body weight. The G-allele confers a ~1.3x increased obesity risk. However, the SNP showing the strongest association with body weight (i.e. body mass index, BMI) is not rs17817449, although this SNP is one of co-inherited SNPs in the FTO gene region. 
rs10830963(G;G) -> www.snpedia.com/index.php/rs10830963
rs13266634(C;T) -> www.snpedia.com/index.php/rs13266634
rs1801282(C;G) -> www.snpedia.com/index.php/Rs1801282
rs17817449(T;G) -> www.snpedia.com/index.php/Rs17817449

Leicht erhöhtes Risiko für verschiedene Krebsarten:

rs944289(T;T) Schilddrüsenkrebs
Each T at rs944289 increased the odds of thyroid cancer by 1.37 times. -> slightly increased risk for thyroid cancer.
www.snpedia.com/index.php/Rs944289
blog.23andme.com/23andme-research/snpwatch/snpwatch-two-gene-variations-linked-to-thyroid-cancer/

rs6983267(G;T) Prostatakrebs & Darmkrebs
rs6983267(G>T) is a SNP on chromosome 8q24, associated with increased risk for several cancers, particularly prostate cancer. This SNP has also been reported to influence the cancer- decreasing-risk effect of aspirin in patients with colon cancer. www.nejm.org/doi/full/10.1056/NEJMoa075819
www.snpedia.com/index.php/Rs6983267

rs910873(A;G) Melanom & Plattenepithelkarzinom
rs910873(G>A) has been associated with an 1.7x increased risk of melanoma and an increased risk of squamous cell carcinoma in dominant models (G;A or A;A; dominant) 
www.snpedia.com/index.php/Rs910873

rs10974944(C;G) & rs12340895(C;G) Erhöhtes Risiko für myeloproliferative Neoplasien (chronischen Bluterkrankungen):
rs10974944 is located in the JAK2 gene which appears to predispose to V617F-positive neoplasms; The SNP was associated with a 4-fold increased odds of V617F-associated MPNs.   rs12340895(C>G). People with a G at rs12340895 have about two times the odds of developing V617F-positive MPN compared to people without the disease. have about three times higher odds of developing V617F-positive MPN compared to individuals without the A version."
www.snpedia.com/index.php/rs12340895

rs5888(C;T) Erhöhtes Risiko für Altersblindheit
rs5888 is a SNP in the scavenger receptor class B, member 1 SCARB1 gene. In a case-control study of two Caucasian populations totaling 2,498 patients, rs5888(C;T) heterozygotes had an increased odds ratio of 2.9 (CI: 1.6-5.3, p<0.002) for age-related macular degeneration. http://www.snpedia.com/index.php/Rs5888

rs2070744(T;T)
rs2070744(T>C). This SNP is located in the in the promoter region of the NOS3 gene which encodes nitric oxide synthase 3. The SNP has been associated with higher levels of the corresponding mRNA (and possibly protein). The risk allele (C) of this SNP was found associated with: Rheumatoid Arthritis and cardiovascular mortality in high-risk patients. Progression (but not occurrence) of prostate cancer in high frequency in male athletes from power sports such as jumpers, throwers, and sprinters. 
https://www.snpedia.com/index.php/Rs2070744                                                   

rs6152(A;A) Reduziertes Risiko für männliche Glatzenbildung 
rs6152(G>A), located in the first exon of the androgen receptor AR gene on the X chromosome, is highly indicative of the ability to develop male pattern baldness. The risk allele is (G). However, although it appears to be necessary for baldness to develop, other (as yet unknown) variations must also be present for baldness to actually occur. Since this SNP is on the X chromosome, and affects a trait primarily seen only in males, a single allele is shown as representing the individual's genotype. However, baldness may also occur in females, presumably only in females homozygous for rs6152(G;G) and also harboring the (as yet unknown) additional variations required for baldness.
www.snpedia.com/index.php/Rs6152 
www.nature.com/ng/journal/v40/n11/full/ng.255.html

rs1799971(A;G) Möglicherweise erhöhtes Risiko für Alkohol/Heroin-Abhängigkeit 
The rs1799971(G) allele in exon 1 of the mu opioid receptor OPRM1 gene causes the amino acid asparagine (Asn) at residue 40, to be replaced by aspartic acid (Asp). Carriers of at least one rs1799971(G) allele appear to have stronger cravings for alcohol than carriers of two rs1799971(A) alleles, and are thus possibly at higher risk for alcoholism. However, research results are mixed, and there are studies both agreeing or disagreeing with this finding. 
www.snpedia.com/index.php/Rs1799971

Charaktereigenschaften:

rs4680(A;A)
rs4680(G>A) is a well studied SNP in the COMT gene. The COMT gene codes for the COMT enzyme, which breaks down dopamine in the brain's prefrontal cortex. The wild-type allele is a (G), coding for a valine amino acid; the (A) substitution polymorphism changes the amino acid to a methionine. This alters the structure of the resultant enzyme such that its activity is only 25% of the wild type. As a result, A allele carriers have more dopamine in their prefrontal cortex, which may be responsible for many of the neuropsychological associations listed below. rs4680(A) = Worrier. Lower COMT enzymatic activity, therefore higher dopamine levels; lower pain threshold, enhanced vulnerability to stress, yet also more efficient at processing information under most conditions. rs4680(G) = Warrior. higher COMT enzymatic activity, therefore lower dopamine levels; higher pain threshold, better stress resiliency, albeit with a modest reduction in executive cognition performance under most conditions. 
http://www.snpedia.com/index.php/Rs4680

rs53576(G;G) -> Optimistic and empathetic; handle stress well
rs53576(A>G). Studies have demonstrated that individuals with the G allele are more empathetic, feel less lonely, employ more sensitive parenting techniques, and have lower rates of autism
http://www.snpedia.com/index.php/Rs53576

rs17070145(C;T) -> Increased memory performance
Carriers of an rs17070145 T allele had 24% better free recall performance 5 min after word presentation (P = 0.000004) and 19% better free recall performance 24 hours after word presentation (P = 0.0008) than did noncarriers
www.snpedia.com/index.php/Rs17070145
www.ncbi.nlm.nih.gov/clinvar/variation/1213/

Überträger-Status für genetische Erkrankungen
(diese Varianten verursachen genetische Krankheiten, wobei die Person selbst nicht erkrankt, aber eine Vererbung an Nachkommen möglich ist)

rs11549407(C;T) Beta Thalassemia carrier
Hemoglobin beta-zero mutation; anemia possible (es können zusätzlich schwache Symptome auftreten: Anämie/Blutarmut, leicht vergrößerte Milz). HBB:uc001mae.1:exon2:c.118C>T:p.(Gln40*), rs11549407. Der Teilnehmer hat eine Mutation im Hämoglobin-Gen HBB, welches für den Sauerstofftransport in roten Blutkörperchen wichtig ist. Zum Glück ist nur eine der beiden Kopien dieses Gens betroffen, so dass dieser Gendefekt außer gewissen Einschränkungen beim Ausdauersport keine negativen Auswirkungen hat. Außerdem schützt diese Mutation teilweise gegen Malaria, weswegen sie bei Personen aus heutigen oder historischen Malariagebieten (in diesem Fall: die Po-Ebene in Norditalien) weit verbreitet ist.
www.ncbi.nlm.nih.gov/clinvar/variation/15402/
www.snpedia.com/index.php/Rs11549407

Seltene genetische Varianten mit unklarer Interpretation (diese genetischen Varianten sind so selten, dass es zwar Hinweise auf ihre mögliche Auswirkungen gibt, aber keine sichere Aussage möglich ist)

Möglicherweise erhöhtes Risiko für verschiedene Krebsarten

CDKN2A:uc003zpl.3:exon2:c.382G>A:p.(Ala128Thr), rs575031539 -> Hereditary cancer-predisposing syndrome (uncertain significance).

The CDKN2A gene encodes proteins that regulate 2 critical cell cycle regulatory pathways, the p53 (TP53; 191170) pathway and the RB1 (614041) pathway. Through the use of shared coding regions and alternative reading frames, the CDKN2A gene produces 2 major proteins: p16(INK4), which is a cyclin-dependent kinase inhibitor, and p14(ARF), which binds the p53-stabilizing protein MDM2.
www.ncbi.nlm.nih.gov/clinvar/variation/142725/
www.omim.org/entry/600160

Möglicherweise erhöhtes Risiko für Nierenschäden
FN1:uc002vfa.3:exon29:c.4631A>T:p.(Asp1544Val) -> Glomerulopathy with fibronectin deposits. Fibronectin-1 belongs to a family of high molecular weight glycoproteins that are present on cell surfaces, in extracellular fluids, connective tissues, and basement membranes. Fibronectins interact with other extracellular matrix proteins and cellular ligands, such as collagen, fibrin, and integrins. Fibronectins are involved in adhesive and migratory processes of cells. Two major forms of fibronectin exist: a plasma soluble form and a cellular form. Alternatively spliced FN1 EDA and EDB are prominently expressed during wound healing, lung, liver and kidney fibrosis, vascular intimal proliferation, and cardiac transplantation. Glomerulopathy with Fibronectin Deposits 2. In patients with glomerulopathy with fibronectin deposits 3 heterozygous mutations in the FN1 gene were identified.
www.omim.org/entry/135600

Genomdaten

Alle Daten der Genomsequenzierung sind öffentlich verfügbar und können in verschiedenen Formaten angeschaut und heruntergeladen werden.

Die untenstehenden Links stellen das Genom zum Download zur Verfügung. Die ersten beiden Links enthalten die Sequenzierungsdaten geordnet nach ihrem Auftreten in den Chromosomen des menschlichen Referenz-Genoms. Die drei folgenden Links enthalten die Positionen, in denen sich das Genom vom Referenz-Genom unterscheidet. Alle Daten beziehen sich auf die hg19/GRCh37 Version des menschlichen Referenz-Genoms.

Genom herunterladen - alle Details

PGA1_sequences.bam  Sequenzierungsdaten (Achtung: diese Datei ist sehr groß, BAM-Format, Dateigröße ca. 150 GB)
PGA1_sequences.bai Indexdatei für die Sequenzierungsdaten

PGA1_variants.vcf.gz Genetische Varianten
PGA1_variants.vcf.gz.tbi Indexdatei für genetische Varianten

PGPC1_variants.tsv Genetische Varianten in einem vereinfachten Textformat, das mit einigen web-basierten Analyse-Werkzeugen kompatibel ist

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