OMIA:002700-9615 : Hyposegmentation of granulocytes in Canis lupus familiaris (dog)
Categories: Haematopoietic system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 610007 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: unknown
Key variant known: yes
Year key variant first reported: 2023
Cross-species summary: This phenotype is characterized by hyposegmented nuclei of granulocytes. The phenotype resembles Pelger-Huët anomaly, but is caused by variants in the LMBR1L gene.
Species-specific description: The phenotype has initially been termed Pelger-Huët anomaly due to the phenotypic similarity with human Pelger-Huët anomaly. However, the human Pelger-Huët anomaly is caused by variants in the LBR gene, while this entry refers to an LMBR1L-related phenotype characterized by hyposegmented granulocytes.
History: Due to the phenotypic similarity with human Pelger-Huët anomaly, Latimer et al. (2000) initially hypothesized about an autosomal semidominant inheritance with embryonic lethality in homozygous mutant dogs.
With the identification of the causative genetic variant in the LMBR1L gene, an autosomal recessive mode of inheritance has been conclusively established. The trait is probably not associated with any gross health problems and is not homologous to human Pelger-Huët anomaly.
Mapping: Lourdes Frehner et al. (2023): "Genome-wide association mapped the HG locus to chromosome 27 and established an autosomal recessive mode of inheritance. "
Molecular basis: Lourdes Frehner et al. (2023): "Whole genome sequencing identified a splice site variant in LMBR1L, c.191+1G>A, as most likely causal variant for the HG phenotype. The mutant allele abrogates the expression of the longer X2 isoform but does not affect transcripts encoding the shorter X1 isoform of the LMBR1L protein."
Prevalence: Lourdes Frehner et al. (2023): "The homozygous mutant LMBR1L genotype associated with HG is common in Australian Shepherd Dogs and was found in 39 of 300 genotyped dogs (13%)."
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|LMBR1L||limb development membrane protein 1-like||Canis lupus familiaris||27||NC_051831.1 (5526748..5539570)||LMBR1L||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1583||Australian Shepherd||Hyposegmentation of granulocytes||LMBR1L||splicing||Naturally occurring variant||UU_Cfam_GSD_1.0||27||g.41169674C>T||c.191+1G>A||XM_038577534.1||2023||37347778|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2023||Lourdes Frehner, B., Christen, M., Reichler, I.M., Jagannathan, V., Novacco, M., Riond, B., Peters, L.M., Suárez Sánchez-Andrade, J., Pieńkowska-Schelling, A., Schelling, C., Kipar, A., Leeb, T., Balogh, O. :|
|Autosomal recessive hyposegmentation of granulocytes in Australian Shepherd Dogs indicates a role for LMBR1L in myeloid leukocytes. PLoS Genet 19:e1010805, 2023. Pubmed reference: 37347778 . DOI: 10.1371/journal.pgen.1010805.|
|2000||Latimer, K.S., Campagnoli, R.P., Danilenko, D.M. :|
|Pelger-Huet anomaly in Australian shepherds: 87 cases (1991-1997) Comparative Haematology International 10:9-13, 2000.|
|1989||Latimer, K.S., Kircher, I.M., Lindl, P.A., Dawe, D.L., Brown, J. :|
|Leukocyte function in Pelger-Huët anomaly of dogs. J Leukoc Biol 45:301-10, 1989. Pubmed reference: 2649629 . DOI: 10.1002/jlb.45.4.301.|
- Created by Tosso Leeb on 16 May 2023
- Changed by Tosso Leeb on 16 May 2023
- Changed by Imke Tammen2 on 25 Jun 2023