Unser Haushund: Eine Spitzmaus im Wolfspelz? - Wolf-Ekkehard ...
Teilen Einbetten Melden
ePaper herunterladen

Unser Haushund: Eine Spitzmaus im Wolfspelz? - Wolf-Ekkehard ...

Unser Haushund: Eine Spitzmaus im Wolfspelz? - Wolf-Ekkehard ... Unser Haushund: Eine Spitzmaus im Wolfspelz? - Wolf-Ekkehard ...

weloennig.de
13.07.2015 Aufrufe

160D. h. der wesentliche Teil der "403 CNVs that overlap 401 genes, which areenriched for defense/immunity, oxidoreductase, protease, receptor, signalingmolecule and transporter genes" kommt beim Wolf selbst vor (siehe Figure 3 undAusführungen dazu in Nicholas et al. 2009, p. 494 – wie oben zitiert).4. Zur Frage nach CNVs and breed specificity kommentieren Berglund et al.(2012, p. 16):"The two breeds for which ten individuals were analysed were selected for their large (Golden Retriever)and small (Irish Wolfhound) population sizes, respectively. We first attempted to see how many CNVswere present in all ten dogs of a breed, suggesting fixation (Table 7). For Golden Retrievers 20 CNVs werepresent in all dogs and for Irish Wolfhounds 38 CNVs appeared fixed, possibly reflecting the slightlyhigher degree of inbreeding in Irish Wolfhounds. A much smaller number of breed-specific loci wereidentified, and no cases of breed specific fixed CNVs were identified in these deeply sampled breeds.The relative lack of breed specific fixed CNVs suggests that instances of those involved in breed-specificphenotypes must be rare. Overall the CNV frequency distributions appear qualitatively similar tothose expected for neutral polymorphisms.”Berglund et al. berichten uns zu ihrer Suche nach breed-specific characteristicsweiter von 3 verschiedenen Deletionen, die als gute Kandidaten in Frage kommen,wenn sie fortfahren (2012, pp. 16/17):"We scanned our dataset for CNVs that were fixed for one allele in some two-sample breeds and anotherallele in all other two-sample breeds (i.e. are not polymorphic in any breed). There are 24 such CNVs, ofwhich all but one is specific to a single breed. This CNV is a 12.7 kb deletion (located at 55.5 Mb onchromosome 6) shared by Cavalier King Charles Spaniel and English Springer Spaniel, whichoverlaps the gene DPYD that encodes the enzyme dihydropyrimidine dehydrogenase (DPD) involvedin pyrimidine catabolism. Examples of breed-specific fixations include a 32.7 kb deletion on chromosome28 in German Shepherds downstream of DUSP10, which is involved in immune responses and mediatesvarious physiological processes, and a 18.1 kb deletion on chromosome 21 in Finnish Spitz immediatelydownstream of CYP2R1 (cytochrome p450, family 2, subfamily R, polypeptide 1) and overlapping PDE3B(phosphodiesterase 3B, cGMP-inhibited). These regions are good candidates for governing breed-specificcharacteristics, although further investigation is necessary to determine if they are really fixed, or have anyphenotypic effect.”5. Wenn auch die gefundenen Steigerungen und Verringerungen in derGenkopienzahl bislang keinem bestimmten Phänotyp zugeordnet werdenkönnen, der Hunderassen definieren würde, so erwähnen sowohl Nicholas et al.(2011) als auch Berglund et al. (2012) mehrere potentielle Kandidaten für dieweitere Forschung; dabei könnten Deletionen (auch im Vergleich zum Wolf)eine besondere Rolle zu spielen.Ein paar weitere Beispiele aus Nicholas et al. (2009, pp. 491, 492/493; manbeachte bitte wieder die Richtungsfrage – Aufbau und/oder Abbau vonFunktionen? – durch die CNVs bedingten Veränderungen):P. 494: "Gene content of CNV regions. […] For example, in humans, copy number variation of cytochromeP450 genes, such as CYP2D6, contributes to interindividual variation in drug metabolism phenotypes (Daly2004; Ledesma and Agundez 2005; Ouahchi et al. 2006). Similar to humans, adverse drug responses havebeen described in dogs, which often show marked variation in prevalence between breeds (Hickford et al.2001; Mealey et al. 2001, 2003; Nelson et al. 2003; Neff et al. 2004; Trepanier 2004). Several CYP genesoverlap CNVs, perhaps the most interesting of which is CYP3A12, the canine ortholog to human CYP3A4,which is the most abundant hepatic and intestinal cytochrome P450 isoform and is involved inmetabolizing a substantial fraction of all drugs (Schuetz 2004). Specifically, nine dogs (Afghan Hound,Doberman Pinscher, German Shepherd, Labrador Retriever, Rottweiler, West Highland White Terrier,Yorkshire Terrier, Boxer, and Wolf) show partial loss of CYP3A12, and of these, adverse drug

161responses have been described in Doberman Pinschers (sulfonamide hypersensitivity) (Trepanier 2004),Labrador Retrievers (carprofen-induced hepatic toxicity) (Hickford et al. 2001), and Boxers(acepromazine sensitivity, although this result is controversial) (Wagner et al. 2003). Obviously, theseobservations, while interesting, require additional study to better delimit the relationship between CYP3A12copy number and variation in drug metabolism phenotypes. CNVs that span potential genes influencingdisease susceptibility were also identified. For instance, the glucokinase regulatory protein gene (GCKR)is located in a complex CNV region (Fig. 5). Recent genome-wide association studies in humans havefound that GCKR variation increases susceptibility to type 2 diabetes.Und ergänzend bemerken Nicholas et al. in ihrem Beitrag von 2011, pp. 3/4:Specifically, we define CNV regions that exhibit both gains and losses in copy number within a singleindividual as complex. While only 14 complex regions were identified, they are all from segmentalduplications. […] As shown in Table 3, the average number of CNVs across all individuals was 187,ranging from 40 (in a Beagle and Greyhound) to 332 (in a Standard Poodle).Pp. 5/6: …a CNV region on CFA12 was identified in the Standard Poodle, which contains a number ofgenes, such as PSORS1C2, CDSN, and CCHCR1, that are associated with various epithelial processesand skin disorders (Figure 4). Standard Poodles are a breed marked with common occurrences ofskin disorders or disorders with epithelial symptoms such as Cushing's disease(hyperadrenocorticism) and Sebaceous adenitis. Additionally some skin disorders, such as psoriasis inhumans, have been associated with copy number polymorphisms. Thus, PSORS1C2, CDSN, andCCHCR1 are excellent candidates to pursue in future association studies of skin phenotypes in StandardPoodles. Furthermore, a topoisomerase gene, TOP3B, involved in the cutting of DNA strands duringtranscription and recombination [34], was also found to be polymorphic in six breeds (Alaskan Malamute,Border Collie, Brittany, Labrador Retriever, Shar Pei, and Standard Poodle).[…] A number of interesting genes exist among the top 50 most differentiated CNV regions that may berelevant to phenotypic variation between breeds, such as ATBF1, a zinc finger transcription factor thatregulates neuronal and muscle development [35] and NKAIN2, which is associated with susceptibilityto lymphoma [36], the most common form of canine cancer [37].Siehe den Link zu weiteren Punkte bei den Verfassern.6. Nach den oben aufgeführten Daten, heißt "enriched for” nicht automatischVerbesserung/Bereicherung/positive Weiterentwicklung einer Funktion. Es wirdsogar von "enriched in deletions" gesprochen (Berglund et al. 2012, p. 12 285 ) und"complex" definieren Nicholas et al. wie oben zitiert ("we define CNV regions thatexhibit both gains and losses in copy number within a single individual ascomplex").7. Erinnern wir noch einmal an die Definition der CNVs: "A DNA sequence,1000 nucleotides (or synonymously base pairs) in length or longer, that is present avariable number of times as copies in a genome relative to a reference genome."Wie erwähnt, ist das Referenzgenom in den Untersuchungen von Berglund et al.2012 ein Boxerrüde und in den Studien von Nicholas et al. (2011) eineBoxerhündin, nicht aber der Wolf (pp. 2, 4, 7, 8):"In all of the aCGH hybridizations 286 we used the same reference sample (a female Boxer distinct fromTasha, the Boxer used for generating the canine reference sequence), which was also the reference in our285 Jonas Berglund, Elisa M Nevalainen, Anna-Maja Molin, Michele Perloski, The LUPA Consortium, Catherine André, Michael C Zody, TedSharpe, Christophe Hitte, Kerstin Lindblad-Toh, Hannes Lohi and Matthew T Webster (2012): Novel origins of copy number variation in the doggenome. Genome Biology 2012, 13:R7 http://genomebiology.com/content/pdf/gb-2012-13-8-r73.pdf ("This Provisional PDF corresponds to thearticle as it appeared upon acceptance. Copyedited and fully formatted PDF and full text (HTML) versions will be made available soon.” Zugriffam 17. 11. 2012)286Vgl. http://en.wikipedia.org/wiki/Array-comparative_genomic_hybridization: "Array-comparative genomic hybridization (also CMA,Chromosomal microarray analysis, microarray-based comparative genomic hybridization, array CGH, a-CGH, aCGH) is a technique to detectgenomic copy number variations at a higher resolution level than chromosome-based comparative genomic hybridization (CGH).[1] It can beused to create a virtual karyotype. […] DNA from a test sample and normal reference sample are labelled differentially, using differentfluorophores, and hybridized to several thousand probes. The probes are derived from most of the known genes and non-coding regions of the

160D. h. der wesentliche Teil der "403 CNVs that overlap 401 genes, which areenriched for defense/<strong>im</strong>munity, oxidoreductase, protease, receptor, signalingmolecule and transporter genes" kommt be<strong>im</strong> <strong>Wolf</strong> selbst vor (siehe Figure 3 undAusführungen dazu in Nicholas et al. 2009, p. 494 – wie oben zitiert).4. Zur Frage nach CNVs and breed specificity kommentieren Berglund et al.(2012, p. 16):"The two breeds for which ten individuals were analysed were selected for their large (Golden Retriever)and small (Irish <strong>Wolf</strong>hound) population sizes, respectively. We first attempted to see how many CNVswere present in all ten dogs of a breed, suggesting fixation (Table 7). For Golden Retrievers 20 CNVs werepresent in all dogs and for Irish <strong>Wolf</strong>hounds 38 CNVs appeared fixed, possibly reflecting the slightlyhigher degree of inbreeding in Irish <strong>Wolf</strong>hounds. A much smaller number of breed-specific loci wereidentified, and no cases of breed specific fixed CNVs were identified in these deeply sampled breeds.The relative lack of breed specific fixed CNVs suggests that instances of those involved in breed-specificphenotypes must be rare. Overall the CNV frequency distributions appear qualitatively s<strong>im</strong>ilar tothose expected for neutral polymorphisms.”Berglund et al. berichten uns zu ihrer Suche nach breed-specific characteristicsweiter von 3 verschiedenen Deletionen, die als gute Kandidaten in Frage kommen,wenn sie fortfahren (2012, pp. 16/17):"We scanned our dataset for CNVs that were fixed for one allele in some two-sample breeds and anotherallele in all other two-sample breeds (i.e. are not polymorphic in any breed). There are 24 such CNVs, ofwhich all but one is specific to a single breed. This CNV is a 12.7 kb deletion (located at 55.5 Mb onchromosome 6) shared by Cavalier King Charles Spaniel and English Springer Spaniel, whichoverlaps the gene DPYD that encodes the enzyme dihydropyr<strong>im</strong>idine dehydrogenase (DPD) involvedin pyr<strong>im</strong>idine catabolism. Examples of breed-specific fixations include a 32.7 kb deletion on chromosome28 in German Shepherds downstream of DUSP10, which is involved in <strong>im</strong>mune responses and mediatesvarious physiological processes, and a 18.1 kb deletion on chromosome 21 in Finnish Spitz <strong>im</strong>mediatelydownstream of CYP2R1 (cytochrome p450, family 2, subfamily R, polypeptide 1) and overlapping PDE3B(phosphodiesterase 3B, cGMP-inhibited). These regions are good candidates for governing breed-specificcharacteristics, although further investigation is necessary to determine if they are really fixed, or have anyphenotypic effect.”5. Wenn auch die gefundenen Steigerungen und Verringerungen in derGenkopienzahl bislang keinem best<strong>im</strong>mten Phänotyp zugeordnet werdenkönnen, der Hunderassen definieren würde, so erwähnen sowohl Nicholas et al.(2011) als auch Berglund et al. (2012) mehrere potentielle Kandidaten für dieweitere Forschung; dabei könnten Deletionen (auch <strong>im</strong> Vergleich zum <strong>Wolf</strong>)eine besondere Rolle zu spielen.Ein paar weitere Beispiele aus Nicholas et al. (2009, pp. 491, 492/493; manbeachte bitte wieder die Richtungsfrage – Aufbau und/oder Abbau vonFunktionen? – durch die CNVs bedingten Veränderungen):P. 494: "Gene content of CNV regions. […] For example, in humans, copy number variation of cytochromeP450 genes, such as CYP2D6, contributes to interindividual variation in drug metabolism phenotypes (Daly2004; Ledesma and Agundez 2005; Ouahchi et al. 2006). S<strong>im</strong>ilar to humans, adverse drug responses havebeen described in dogs, which often show marked variation in prevalence between breeds (Hickford et al.2001; Mealey et al. 2001, 2003; Nelson et al. 2003; Neff et al. 2004; Trepanier 2004). Several CYP genesoverlap CNVs, perhaps the most interesting of which is CYP3A12, the canine ortholog to human CYP3A4,which is the most abundant hepatic and intestinal cytochrome P450 isoform and is involved inmetabolizing a substantial fraction of all drugs (Schuetz 2004). Specifically, nine dogs (Afghan Hound,Doberman Pinscher, German Shepherd, Labrador Retriever, Rottweiler, West Highland White Terrier,Yorkshire Terrier, Boxer, and <strong>Wolf</strong>) show partial loss of CYP3A12, and of these, adverse drug

logo

Produkte

Ressourcen

Unternehmen

AGB
Datenschutzerklärung
Cookie-Richtlinien
Cookie-Einstellungen
Impressum
Change language
Made with love in Switzerland
© 2024 Yumpu.com all rights reserved

Hurra! Ihre Datei wurde hochgeladen und ist bereit für die Veröffentlichung.

Erfolgreich gespeichert!

Leider ist etwas schief gelaufen!