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PGA2: Weiblich, etwa 70 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.

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!)

Mögliche Nebenwirkungen bei einigen weit verbreiteten Medikamenten durch eine genetisch bedingt langsame Verstoffwechselung.
Impaired NSAID drug metabolism, which is a risk factor for gastrointestinal bleeding when taking any of these medications: aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib. Der Genotyp umfasst CYP2C8*3 (rs11572080 and rs10509681) CYP2C9*2 (rs1799853) CYP2C9*3 (rs1057910) Als Risikoallele wurden rs1799853(T), rs1057910(C), (rs11572080(A), und rs10509681(C) identifiziert. Mindestens ein Risikoallel ist bei der Probandin nachweisbar. www.snpedia.com/index.php/Gs191

Möglicherweise Nebenwirkungen bei Medikamenten, die die Immunabwehr unterdrücken rs1800460(A;G). rs1800460 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1800460(A), and when it is the only variation in the TPMT gene, it encodes the TPMT*3B allele. This SNP is more common in Caucasians (4.5% of all alleles) than in African-Americans (0.8%). rs1800462(C;G) rs1800462, also known as A80P, is a rare SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP (in orientation to the dbSNP entry) is rs1800462(C), and it encodes the TPMT*2 allele. It may occur at a frequency of 1 in 200 alleles among Caucasians. Thiopurine drugs metabolized by TPMT include azathioprine, mercaptopurine, and thioguanine Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment.
www.snpedia.com/index.php/Rs1800460
www.snpedia.com/index.php/Rs1800462
www.ncbi.nlm.nih.gov/clinvar/variation/37126/
www.ncbi.nlm.nih.gov/books/NBK100661/

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

Genetisch verringerte Werte für LDL-Cholesterin und geringeres Risiko von Herz-Kreislauf-Erkrankungen:

rs11591147(G;T)
rs11591147 is a SNP in the PCSK9 gene. The T-allele is associated with lower LDL cholesterol levels & two to three fold lower risk for both early- and late-onset cardiovascular disease. In a study on over 300,000 individuals rs11591147 was the SNP with the greatest effect on LDL-C and cardiovascular risk reduction. www.snpedia.com/index.php/Rs11591147
www.ncbi.nlm.nih.gov/clinvar/variation/2878/

rs3732379(T;T)
rs3732379(C>T) is a polymorphisms in the chemokine receptor gene CX3CR1. This gene polymorphisms in combination with clinical and demographic factors predicts late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era. The polymorphism has also been reported as one of several polygenic host components that regulates the progression to clinical AIDS in HIV-1-infected individuals. www.ncbi.nlm.nih.gov/clinvar/variation/8152/
science.sciencemag.org/content/287/5461/2274.long

rs1801133(T;T)
rs1801133(C>T) is a SNP that is relatively common and has been studied extensively. It encodes a variant in the MTHFR gene also known as C677T, Ala222Val, and A222V, which encodes an enzyme involved in folate metabolism. Homozygous rs1801133(T;T) individuals have ~30% of the expected MTHFR enzyme activity, resulting in high homocysteine, low B12 and folate levels. Moderately increased odds of having a child with a neural tube defect. Slightly increased risk for several other diseases. Research on MTHFR-influenced health conditions have been inconclusive or conflicting. Based on the existing data, people should not interpret their genotypes at the common MTHFR variants as having an effect on their health.
www.snpedia.com/index.php/Rs1801133(T;T)
www.snpedia.com/index.php/Rs1801133
www.ncbi.nlm.nih.gov/clinvar/variation/3520/

rs1799930(A;A) Leicht erhöhtes Risiko für Schwerhörigkeit im Alter
rs1799930(G>A) is a SNP in the NAT2 gene, potentially encoding a variant detoxifying protein known as an N-acetyltransferase. Other NAT2 SNPs are known which are also inherited. The risk allele for this SNP is rs1799930(A). For homozygous A-allele carriers a 2.8-fold increased risk of Age Related Hearing Impairment (ARHI) has been reported.
www.snpedia.com/index.php/Rs1799930
www.ncbi.nlm.nih.gov/pubmed/17513527
www.ncbi.nlm.nih.gov/pubmed/16369173

Leicht 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.
·         rs1061170 is a SNP in the complement factor H CFH gene. The rs1061170(T) allele encodes the more common Tyr (Y), while the generally rarer rs1061170(C) encodes the His (H). This SNP has been associated with a 2.5-fold increased risk for age related macular degeneration.
·         rs3775291 is a SNP in the TLR3 gene associated with an amino acid change in the corresponding protein. rs3775291(G>A) has been associated with a 0.7-fold reduced risk of "dry" age related macular degeneration (ARMD).
www.snpedia.com/index.php/Rs5888 (increased risk)
www.snpedia.com/index.php/Rs1061170 (increased risk)
www.snpedia.com/index.php/Rs3775291 (decreased risk)

rs17070145(T;T) Genetisch bedingte deutlich höhere Gedächtnisleistung
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. T allele carriers performed significantly better than noncarriers.
www.snpedia.com/index.php/Rs17070145
www.ncbi.nlm.nih.gov/clinvar/variation/1213/

rs1815739(C;C) Better performing muscles
the rs1815739(C>T) SNP is located in the ACTN3 gene and encodes a premature stop codon in a muscle protein called alpha-actinin-3. The homozygous T;T genotype is under-represented in elite strength athletes, consistent with previous reports indicating that alpha-actinin-3 deficiency appears to impair muscle performance. This genotype indicates better performing muscles, particularly for sprinting and power sports. However, some studies failed to replicate the data.
www.snpedia.com/index.php/Rs1815739

rs2070744(T;T)
rs2070744(T>C) is located in the promoter region of the NOS3 gene which encodes nitric oxide synthase 3. The C-allele, which is rare in the Caucasian population, is associated with higher levels of the corresponding mRNA and associations with: rheumatoid Arthritis, cardiovascular mortality in high-risk patients, and progression (but not occurence) of prostate cancer. Men who carry the C allele responded more favorably to the antihypertensive effects of aerobic exercise.
www.snpedia.com/index.php/Rs2070744(T;T)

Genetische Variante, die mit trockenem Ohrenschmalz und reduziertem Körpergeruch einhergeht (besonders verbreitet bei Personen aus Ostasien):

rs17822931(T;T) Dry earwax
rs17822931(C>T) is a SNP in the ATP-binding cassette, sub-family C (CFTR/MRP), member 11 ABCC11 gene. The ABCC11 protein helps to transport small molecules across apical membranes such as those in apocrine secretory cells. This SNP determines wet vs dry earwax as well as sweat production. The majority of Europeans are homozygous CC while Asians are homozygous TT. rs17822931(T;T) individuals were at least 5-fold less likely to use deodorant.
www.snpedia.com/index.php/Rs17822931

(Background: Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. The ABCC11 gene is responsible for determination of earwax type. Geographical data suggest that the T-allele arose in northeast Asia and thereafter spread through the world. Migration of humans can be traced using the ABCC11 gene alleles. A simulation experiment using a pseudo-sampling variable revealed that the mutation of rs17822931-T occurred 2006 generations (ca. 40.000 years) ago in an ancient northern Mongoloid tribe. Assuming a recessive selection model, a coalescent-based simulation approach suggested that the selection coefficient of rs17822931-T had been approximately 0.01 in the East Asian population. The selective advantage of rs17822931-T was apparently related to an adaptation to cold climate. The results provide a striking example of how local adaptation has played a significant role in the diversification of human traits, that followed a spread of the dry ear wax allele to other regions of Asia via migration of the ancient tribe.)
https://en.wikipedia.org/wiki/ABCC11#Demographics) Ohashi J et al. Mol Biol Evol. 2011;28:849-5

rs10246939(T;C), rs1726866(T;C), rs713598(G;C) Wahrnehmung von bitterem Geschmack
The 3 SNPs are located in the gene TAS2R38. You are heterozygous at all 3 of the SNPs which are known to influence the ability to taste bitterness. This means you are better than average at detecting bitter tastes while young, but that this ability will decrease to less than average during adulthood. As a child you will probably hate brussel sprouts, and by early adulthood will discover that olives and brussel sprouts now taste good. In 2010, a study showed that the change of bitter sensitivity over the lifespan (from bitter sensitive to less so) is more common in people with this genoset. www.snpedia.com/index.php/Gs227

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

Trägerin einer genetischen Veränderung, die mit Mikrophthalmie zusammenhängt (einer Störung der Augenentwicklung) PRSS56:uc021vyh.1:exon8:c.904G>T:p.(Val302Phe), rs74703359 -> Carrier status for autosomal recessive microphthalmia (Microphthalmia, isolated 6).
Microphthalmia is an eye abnormality that arises before birth. The inheritance is autosomal recessive. In microphthalmia, one or both eyeballs are abnormally small. In individuals affected with severe disease the eyeball may be completely missing; however, even in these cases some remaining eye tissue is generally present. Microphthalmia may or may not result in significant vision loss..People with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision. People with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). https://ghr.nlm.nih.gov/condition/microphthalmia www.ncbi.nlm.nih.gov/clinvar/variation/183171/
www.omim.org/entry/613858
www.ncbi.nlm.nih.gov/pubmed/21850159

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)

Malignant hyperthermia susceptibility (MHS) rs147136339(A;G) Die genetische Variante führt möglicherweise zu einem erhöhten Risiko für eine schwere Narkose-bedingte Komplikation (allerdings ist die Variante in der Bevölkerung häufiger als die Erkrankung, daher ist eine Kausalität eher unwahrscheinlich).

One form of malignant hyperthermia (MHS1) is caused by heterozygous mutation in the ryanodine receptor gene (RYR1; 180901) on chromosome 19q13. RYR1:uc002oit.3:exon86:c.11798A>G:p.(Tyr3933Cys), rs147136339 Malignant hyperthermia susceptibility (MHS), a skeletal muscle disorder most often inherited as an autosomal dominant trait, is one of the main causes of death due to anesthesia. In susceptible people, a malignant hyperthermia episode is triggered by exposure to commonly used volatile anesthetic agents such as halothane or depolarizing muscle relaxants such as succinyl choline. A fulminant MH crisis is characterized by any combination of hyperthermia, skeletal muscle rigidity, tachycardia or arrhythmia, respiratory and metabolic acidosis, and rhabdomyolysis. Except for this susceptibility to triggering agents, MHS patients are not clinically distinguishable from the general population. Anaesthesia for known MH susceptible patients requires avoidance of triggering agents (all volatile anaesthetic agents and succinylcholine). All other drugs are safe (including nitrous oxide), as are regional anaesthetic techniques.
www.ncbi.nlm.nih.gov/clinvar/variation/133021/
www.omim.org/entry/145600

CDH1:uc002ewg.1:exon15:c.2336G>A:p.(Arg779Gln), rs587781311
Die genetische Variante führt möglicherweise zu einem erhöhten Risiko für Magenkrebs (unklare Datenlage, eher unwahrscheinlich) CDH1 cadherin gene. The CDH1 gene encodes E-cadherin, a calcium ion-dependent cell adhesion molecule that functions in the establishment and maintenance of epithelial cell morphology during embryogenesis and adulthood. Development of malignant tumors is in part characterized by the ability of a tumor cell to overcome cell-cell adhesion and to invade surrounding tissue. E-cadherin, the main adhesion molecule of epithelia, has been implicated in carcinogenesis because it is frequently lost in human epithelial cancers. Heterozygous CDH1 mutation carriers have a 70 to 80% lifetime risk of developing diffuse gastric cancer. In addition to gastric cancer, up to 60% of female mutation carriers develop lobular carcinoma of the breast, and some carriers may develop colorectal cancer. Identification of mutation carriers is important, because the characteristic microscopic foci of signet ring cell adenocarcinoma in HDGC usually involves the submucosa and is often not readily detectable by routine upper endoscopy screening (summary by Fitzgerald et al., 2010). Hereditary diffuse gastric cancer is an autosomal dominant cancer predisposition syndrome.
www.ncbi.nlm.nih.gov/clinvar/variation/140840/
www.omim.org/entry/192090

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

PGA2_sequences.bam  Sequenzierungsdaten (Achtung: diese Datei ist sehr groß, BAM-Format, Dateigröße ca. 150 GB)
PGA2_sequences.bai Indexdatei für die Sequenzierungsdaten

PGA2_variants.vcf.gz Genetische Varianten
PGA2_variants.vcf.gz.tbi Indexdatei für genetische Varianten

PGA2_variants.tsv Genetische Varianten in einem vereinfachten Textformat, das mit einigen web-basierten Analyse-Werkzeugen kompatibel ist

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