Albino Research Articles

Skin Pigmentation Differences between Mongolian, Korean, and Uzbekistan Ancient Human DNA Samples

Background This study reports the use of real-time PCR to identify the SNP rs1545397 in the intron region on the OCA2 gene from ancient and degraded DNA isolated from ancient human bones from Mongolia, Korea, and Uzbekistan. This SNP is a marker for skin pigmentation. LightCycler-based probes (HybProbes) were designed. A LightCycler (version 2.0) system was used for the real-time PCR. Results The results of the real-time PCRs of three different genotypes of SNP rs1545397 were compared with those of the direct sequencing. Melting curve analysis was used for genotype determination. Three genotypes were distinguished: the homozygous T (T/T) SNP type formed a distinct melting peak at 53.3 ± 0.14°C, the homozygous A (A/A) SNP type formed a distinct melting peak at 57.8 ± 0.12°C, and the heterozygous A/T SNP type formed two distinct melting peaks at 53.3 ± 0.17°C and 57.8 ± 0.15°C. Mongolian aDNA samples tested in this study carried all three types of the SNP (A/T, A/A, and T/T) with no distinctly predominant type observed. In contrast, Korean aDNA samples carried the Asian genotype (T/T), while the Uzbekistan aDNA samples carried the European genotype (A/A) more often than the Asian genotype (T/T). Conclusions Human Mongolian aDNA samples had A/T, A/A, and T/T SNP rs1545397 with no distinct predominant genotype. When combined with the archeological and aDNA studies of other coupling morphologies with aDNA, our results infer that Mongolia's prehistoric population had considerable heterogeneity of skin color and morphological traits and that in the Neolithic period, a Eurasian or mixed population inhabited the western part of Mongolia.

Apple latent spherical virus (ALSV)-induced gene silencing in a medicinal plant, Lithospermum erythrorhizon

Lithospermum erythrorhizon is a medicinal plant that produces shikonin, a red lipophilic naphthoquinone derivative that accumulates exclusively in roots. The biosynthetic steps required to complete the naphthalene ring of shikonin and its mechanism of secretion remain unclear. Multiple omics studies identified several candidate genes involved in shikonin production. The functions of these genes can be evaluated using virus-induced gene silencing (VIGS) systems, which have been shown advantageous in introducing iRNA genes into non-model plants. This study describes the development of a VIGS system using an apple latent spherical virus (ALSV) vector and a target gene, phytoene desaturase (LePDS1). Virus particles packaged in Nicotiana benthamiana were inoculated into L. erythrorhizon seedlings, yielding new leaves with albino phenotype but without disease symptoms. The levels of LePDS1 mRNAs were significantly lower in the albino plants than in mock control or escape plants. Virus-derived mRNA was detected in infected plants but not in escape and mock plants. Quantitative PCR and deep sequencing analysis indicated that transcription of another hypothetical PDS gene (LePDS2) also decreased in the defective leaves. Virus infection, however, had no effect on shikonin production. These results suggest that virus-based genetic transformation and the VIGS system silence target genes in soil-grown L. erythrorhizon.

Albinism in plants - far beyond the loss of chlorophyll: Structural and physiological aspects of wild-type and albino royal poinciana (Delonix regia) seedlings.

The partial or complete loss of chlorophylls, or albinism, is a rare phenomenon in plants. In the present study, we provide the first report of the occurrence in albino Delonix regia seedlings and describe the morpho-physiological changes associated with albinism. Wild-type (WT) and albino seedlings were characterized. Leaflets samples were processed following common procedures for analysis with light, scanning and transmission electron microscopy. The chlorophyll a fluorescence parameters and the carbohydrate, lipid and soluble protein content were also determined in leaf and cotyledon samples of both albino and WT seedlings. Albino seedlings showed reduced growth. They also had lower chlorophyll and protein content in foliar tissues than WT seedlings, in addition to lower concentrations of lipids and carbohydrates stored in cotyledons. The chloroplasts of albino seedlings were poorly developed, with an undefined internal membrane system and the presence of plastoglobules. Wild-type seedlings had a uniseriate and hypoestomatic epidermis. The mesophyll was dorsiventral, consisting of a layer of palisade parenchyma and two to four layers of spongy parenchyma. In albino seedlings, the spongy parenchyma was compact, with few intercellular spaces, and the thickness of the mesophyll was larger, resulting in increased thickness of the leaf blade. Albino seedlings had higher stomatal density and number of pavement cells, although the stomata had smaller dimensions. In addition to the partial loss of chlorophylls, albino D.regia showed changes at physiological and structural levels, demonstrating the crucial nature of photosynthetic pigments during the development and differentiation of plant leaf tissues/cells.

Platelet δ-Storage Pool Disease: An Update.

Platelet dense-granules are small organelles specific to the platelet lineage that contain small molecules (calcium, adenyl nucleotides, serotonin) and are essential for the activation of blood platelets prior to their aggregation in the event of a vascular injury. Delta-storage pool diseases (δ-SPDs) are platelet pathologies leading to hemorrhagic syndromes of variable severity and related to a qualitative (content) or quantitative (numerical) deficiency in dense-granules. These pathologies appear in a syndromic or non-syndromic form. The syndromic forms (Chediak–Higashi disease, Hermansky–Pudlak syndromes), whose causative genes are known, associate immune deficiencies and/or oculocutaneous albinism with a platelet function disorder (PFD). The non-syndromic forms correspond to an isolated PFD, but the genes responsible for the pathology are not yet known. The diagnosis of these pathologies is complex and poorly standardized. It is based on orientation tests performed by light transmission aggregometry or flow cytometry, which are supplemented by complementary tests based on the quantification of platelet dense-granules by electron microscopy using the whole platelet mount technique and the direct determination of granule contents (ADP/ATP and serotonin). The objective of this review is to present the state of our knowledge concerning platelet dense-granules and the tools available for the diagnosis of different forms of δ-SPD.

SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialization.

Foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialization features such as outer segment lengthening implies reduced foveal cone density, which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype.

Studies on serum level of some trace elements in oculocutaneous albinism subjects in Owerri metropolis

Studies on serum level of some trace elements in oculocutaneous albinism subject in Owerri metropolis was carried out using standard methods. Sixty (60) volunteer subjects made of 30 male and 30 female were used for the study. With the help of syringes, their sera were obtained from their blood samples and used for trace element analysis. Observed results revealed significant (p<0.05) decrease in levels of copper and zinc in male and female oculocutaneous albinism subjects against the control. The mean values for copper and zinc in both male and female also showed significant (p<0.05) reduction when compared to the control. The observed decreased in copper could influence tyrosinase and subsequently melanin production. There is need to investigate the relationship of the pigmentation disorder with other trace elements that were not considered in the present study. This study has revealed the serum level of some trace elements in oculocutaneous albinism subject in Owerri metropolis.

A Histopathological Study of Skin Lesions in Individuals with Oculocutaneous Albinism in Togo in 2019.

Objective The aim of this study was to study the histopathological patterns of skin lesions in persons with albinism (PWA) in Togo in 2019. Method During two mobile skin care clinics in 2019, biopsies/excisional biopsies were performed in PWA in case of clinical doubt or in front of lesions suspected to be cancerous for histological examination. Anatomopathological reports were thus analysed. Results During the two mobile skin care clinics, 115 biopsies/excisional biopsies were carried out in 79 PWA, with a mean age of 24 ± 16.1 years. Histological examination led to a diagnosis in 110 cases (95.6%) and was inconclusive in 5 cases (4 cases of uncertain histological diagnosis and one case of nonspecific histological lesions). Fourteen different histological diagnoses were made, with a frequency ranging from 0.9% (one case) to 26.9% (31 cases). The four most frequent diagnoses in descending order were basal cell carcinomas (BCCs) (31 cases; 26.9%), invasive squamous cell carcinomas (SCCs) or Bowen's disease (23 cases; 20%), keratosis (20 cases; 17.3%), and cysts (seven cases; 6.1%). The 54 skin carcinomas were diagnosed in 33 (41.8%) of the 79 patients who underwent skin biopsies/excisional biopsies. The BCC/SCC ratio was 1.3. No cases of cutaneous melanoma had been diagnosed. Conclusion Skin cancers represent the main histological diagnosis in PWA (46.9%) in Togo in 2019. The pattern of cutaneous malignancies in PWA shows the same trend as that seen in Caucasians with a predominance of basal cell carcinomas.

Identifying and characterizing basal cell carcinomas in persons with albinism.

Historically, persons with albinism (PWA) were thought to develop squamous cell carcinoma (SCC) more frequently than basal cell carcinoma (BCC). Recent evidence suggests BCCs in PWA are more common than initially hypothesized. To characterize the presentation of BCC in PWA. Fifty-four PWA with lesions suspicious for non-melanoma skin cancer sought care at Tanzanian dermatologic clinics from 2017 to 2019. Demographic and clinical presentation data were recorded. Histologic analysis of each sample was completed. The majority of PWA were female (53.7%), with a mean age of 34.6±14.9years and a mean duration of disease of 0.70±0.73years. Physician description of histologically proven BCC included ulceration (41.7%), erythema (16.7%), and scale (16.7%). Lesions were most commonly located on the trunk (47.1%) and face (41.2%). Histologic analysis demonstrated 30.2% of lesions were BCC, 26.4% SCC, and 17% Bowen's disease. Patient population was limited to those visiting clinics, and data were limited by accuracy of the medical record. Basal cell carcinoma occurs at a higher rate than SCC in our population, suggesting BCC in PWA is underdiagnosed. It is important to recognize BCC early in PWA to avoid large disease burden and high rates of morbidity and mortality.

Identification and Computational Analysis of Novel TYR and SLC45A2 Gene Mutations in Pakistani Families With Identical Non-syndromic Oculocutaneous Albinism.

Non-syndromic oculocutaneous albinism (nsOCA) is an inherited disorder of melanin biosynthesis with autosomal recessive mode of inheritance, presenting either hypopigmented or depigmented skin, hair, and eyes. It is genetically heterogeneous with seven loci (OCA1–OCA7) reported to date. In the present study, we have reported three consanguineous families (A, B, C) presenting identical nsOCA phenotypes. Sanger sequencing revealed a novel [NM_000372.5: c.826 T > C, p.(Cys276Arg)] and a recurrent variant [NM_000372.5: c.832C > T, p.(Arg278∗)] in tyrosinase (TYR) in families A and B, respectively. Microsatellite marker-based homozygosity mapping linked family C to OCA4. Sequence analysis identified a novel insertion variant (NM_016180.5: c.1331_1332insA) in the SLC45A2. Further, in silico mutagenesis and dynamic simulation approaches revealed that a novel Cys276Arg variant abolished the cysteine bridge and might contribute toward decreased stability of the TYR protein. Our study expands the mutation spectrum of the TYR and SLC45A2 genes and emphasizes that molecular investigations are essential for accurate disease diagnosis.

Nephro-protective Effect of Clerodendrum infortunatum in Arsenic Induced Sub-acute Toxicity in Albino Rats

The nephro-protective effect of Clerodendrum infortunatum Linn ( C. infortunatum ) in arsenic induced sub-acute toxicity (28 days) was evaluated in albino rats. 18 albino rats were divided into 3 groups representing control, sodium arsenite alone and in combination with hydro-methanolic extract of C. infortunatum leaves representing Group I, Group II and Group III respectively. Sodium arsenite (3 mg/kg b.wt.) and C. infortunatum extracts (100 mg/kg b.wt.) were administered orally once daily over a period of 28 days. At the end of treatment period (29th day), rats were sacrificed. The blood samples for hematological parameters and kidney tissues for oxidative stress indices were collected. The kidney weight was also measured. The preliminary phytochemical screening of the above plant was done to know the different phyto-constituents present. Significant reduction were observed in kidney wt., TEC, Hb% and SOD levels where as creatinine, BUN, TLC and MDA levels (P < 0.001) were significantly increased on arsenic exposure. Treatment with extract of C. infortunatum @ 100 mg/kg b.wt for 28 days, significantly reduced the creatinine, BUN, TLC and MDA levels and significantly increased the kidney wt., TEC, Hb% and SOD level (P ≤ 0.001) as compared to arsenic intoxicated group. The major phyto-constituents were present in the leaves i.e. alkaloids, flavonoids, saponins, sterols and terpenes. On the above findings, it can be concluded that treatment with C. infortunatum in sodium arsenite intoxication has significant role in protecting the animals from nephrotoxicity by modulating hemato-biochemical parameters and oxidative stress level.

Causes of severe visual impairment in infants and methods of management

To examine the causes of severe visual impairment (SVI) in infants below the age of 2 years and to review management methods. The data of 2657 patients followed between January 2014 and July 2019 were reviewed, and 148 (5.6%) infants who had SVI were enrolled. Data including age, gender, affected anatomical site, diagnosis, presence of any non-ophthalmological deficiencies, and methods of management were reviewed. The diagnoses were investigated in the categories of avoidable and unavoidable basis. The methods of management were analysed from the perspective of low vision habilitation. The mean age at first eye examination was 6.61 ± 5.25 months, and 84 (56.7%) infants were male. Of the 148 infants, 69 (46.6%) were premature. Cerebral visual impairment (CVI) was the most common diagnosis in both preterm (39.1%) and term (11.4%) infants. Delayed visual maturation, optic nerve pathologies, oculocutaneous albinism, and congenital cataract were the other frequent causes. The rate of multiple disabilities was 30% in the whole group and 94% in infants with CVI. Most of the babies had a normal-appearing globe (43.3%). Retina was affected in 23.7% of the infants. Avoidable causes were identified in 79.7% of the infants. The used methods of management were optic interventions, visual stimulation therapy, medical and/or surgical treatment. CVI was found the most common cause of SVI in both preterm and term-born infants, and the higher rate of multiple disabilities in these infants was remarkable. Optic interventions and visual stimulation therapy were the most common methods of management.

Spectrum of pathological genetic variants among 405 Chinese pedigrees affected with oculocutaneous albinism

To determine the spectrum of pathological genetic variants among 405 Chinese pedigrees affected with oculocutaneous albinism (OCA). A total of 405 OCA patients were collected. High-throughput sequencing (The panel included TYR, OCA2, TYRP1 and SLC45A2 genes), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to analyze the genetic variants and patterns of each subtype. The overall detection rate of genetic variants was 79.9% (647/810), and the variants included missense variants (57.3%, 371/647), frameshift variants (22.9%, 148/647), nonsense variants (13.9%, 90/647), splicing variants (5.6%, 36/647), and microdeletions (0.3%, 2/647). Thirty-six novel variants were detected. Of the 405 patients, 306 have carried 2 variant alleles (75.6%, 306/405), 35 carried 1 variant alleles (8.6%, 35/405), while no variant was detected in 64 patients. Among the 306 genetically diagnosed OCA patients, OCA1 was the most common form (74.5%, 228/306), compared with OCA2 (15.0%, 46/306), OCA3 (0.7%, 2/306) and OCA4 (9.8%, 30/306), respectively. One patient was found to harbor homozygous c.1262-4_c.1262-3insTAGA variant of the TYRP1 gene. Another patient was found to carry compound heterozygous variants of c.1214C>A (p.T405N) and c.1338delinsCG(p.V447Gfs*19) of the TYRP1 gene. High-throughput sequencing in combination with Sanger sequencing and MLPA can effectively detect genetic variants associated with OCA. Above finding has expanded variant spectrum of OCA, which can facilitate genetic and prenatal diagnosis of this disease in China.

CLINICAL AND HEMATOLOGICAL STUDIES OF CHEDIAKHIGASHI SYNDROM IN IRAQI WATER BUFFALOES (Bubalus bubalis)

Chediack-Higashi syndrome (CHS) is inherited autosomal recessive disorderaffected cattle and other species of animals and caused by LYST gene mutation, andcharacterized by oculocutaneous albinism, variations of total and differentialleukocyte count , different severe infections, dysfunction of platelets and a bleedingtendency.The study included 65 Iraqi water buffaloes of different ages and of bothsexes which was divided as 25 black buffaloes served as controls, 25 buffaloes withpatches or spotted animals and 15 white water buffaloes. The most important clinicalsigned showed by the animals are, white, irregular coat, unpigmented skin, hairs,eyes, with loss of appetite, emaciation, weakness, long hair than normal with tufts,anemia, photophobia with oculocutaneous depigmentation, and dullness. Animals ofboth sexes are affected specially those under one year of age. The results indicated asignificant increases (p<0.05) of body temperatures, pulse and respiratory rate ofdiseased buffalo than in controls, However a significant decrease (P<0.05) has beenregistered in erythrocytes (RBC), hemoglobin concentration (Hb), packed cell volume(PCV) and main corpuscular hemoglobin concentration (MCHC), with no statisticaldifferences was detected in mean corpuscular hemoglobin (MCH), whereas the meancorpuscular volume (MCV) was significantly increase (P<0.05). The results were also show lymphocytosis, eosinophelia and basophelia with Nutropenia andthrombocytopenia with prolonged bleeding time.Conclusion: It has been to ourknowledge that the current study is the first one in this area and the syndrome affectedthe Iraqi buffaloes and caused a clear clinical and hematological signs.

Dermoscopy of Amelanotic Melanoma in a Patient With Oculocutaneous Albinism.

Dermoscopy of Amelanotic Melanoma in a Patient With Oculocutaneous Albinism.

Donskoy cats as a new model of oculocutaneous albinism with the identification of a splice-site variant in Hermansky-Pudlak Syndrome 5 gene.

In the feline Donskoy breed, a phenotype that breeders call "pink-eye," with associated light-brown skin, yellow irises and red-eye effect, has been described. Genealogical data indicated an autosomal recessive inheritance pattern. A single candidate region was identified by genome-wide association study and SNP-based homozygosity mapping. Within that region, we further identified HPS5 (HPS5 Biogenesis Of Lysosomal Organelles Complex 2 Subunit 2) as a strong candidate gene, since HPS5 variants have been identified in humans and animals with Hermansky-Pudlak syndrome 5 or oculocutaneous albinism. A homozygous c.2571-1G>A acceptor splice-site variant located in intron 16 of HPS5 was identified in pink-eye cats. Segregation of the variant was 100% consistent with the inheritance pattern. Genotyping of 170 cats from 19 breeds failed to identify a single carrier in non-Donskoy cats. The c.2571-1G>A variant leads to HPS5 exon-16 splicing that is predicted to produce a 52 amino acids in-frame deletion in the protein. These results support an association of the pink-eye phenotype with the c.2571-1G>A variant. The pink-eye Donskoy cat extends the panel of reported HPS5 variants and offers an opportunity for in-depth exploration of the phenotypic consequences of a new HPS5 variant.

Generation and characterization of four Chediak-Higashi Syndrome (CHS) induced pluripotent stem cell (iPSC) lines.

Chediak-Higashi Syndrome (CHS) is a lysosome-related organelle (LRO) disorder caused by biallelic mutations in the lysosomal trafficking regulator gene, LYST. The clinical features of CHS include oculocutaneous albinism, primary immunodeficiency, bleeding diathesis, risk for development of hemophagocyticlymphohistiocytosis,and progressive neurological problems. The pathophysiological mechanisms underlying this disease are unknown, so developing therapeutic options remains challenging. In this study,four induced pluripotent stem (iPSC) lines from unrelated CHS patients have been generated and successfully characterized for exploring the role of LYST in health and disease in diversecell types.

Mutation Analysis of 63 Northwest Chinese Probands with Oculocutaneous Albinism

ABSTRACT Purpose To identify the mutational spectrum of 63 northwest Chinese probands with Oculocutaneous albinism (OCA), and identify correlations between phenotype and genotype. Methods We recruited 63 clinically diagnosed with OCA patients in Gansu Provincial Maternal and Child Health Care Hospital. Mutation screening analysis was performed by direct sequencing and NGS-target sequencing to screen the variants on genes related to OCA. PolyPhen2 and PROVEN tools were used to predict the possible functional role of the novel variants. We assessed the pathogenicity of the novel mutations according to the clinical interpretation of genetic variants by ACMG/AMP 2015 guideline. Results By molecular testing, 56 of the OCA probands were diagnosed as OCA 1, three were OCA 2 and one was OCA 4. The most common variants of TYR were c.929insC(33.7%), c.896 G > A(12.5%), c.832 C > T(9.6%).We found five novel variants of TYR that have not previously been reported. Conclusions We make an accurate diagnosis and classification for the OCA probands. Our result enlarged the mutational spectrum of TYR and SLC45A2. These findings could be useful for genetic counseling and gene diagnosis of OCA in Northwest of China.

Monosodium Glutamate Level in Kid’s Food and Its Dietary Effects on Liver and Kidney Functions in Adult Rats

Youngsters are inclined to pleasing flavor and express a preference for sweetly, salty, and tasty food items than others. That's why monosodium glutamate (MSG) or tasting salt is using enormously in kid’s food items to increase palatability known as umami taste though it has adverse impacts on health. The purposes of this study were to determine of MSG level in kid’s items such as chips and noodles spices that are randomly taken by them and also its dietary consequences on liver and kidney functions in albino adult rats. The quantitative analysis was done by using the UHPLC system and 36 adult albino rats were used in this study for dietary intervention. The results showed that the overall mean value of MSG in imported chips was about doubled than the local brand. The MSG levels of the noodles spice varied from local to import and brand to brand which extended from 3.87±0.21-7.33±1.62 g/kg. Bodyweight of rats was significantly raised after the oral intervention of about 45.68%, 56.19% substantial in treatment 1(0.5 mg/g body weight of MSG) and treatment 2(1.5 mg/g body weight of MSG) respectively confronted with of about 22.59% in the control group. On regard to liver functions, the level of serum Alanine aminotransferase (ALT) was significantly (p < 0.05) increased but on the contrary, Albumin and Bilirubin were decreased with an uplift of MSG in treated rats compared to the control. MSG had antagonistic impacts on kidney functions as serum creatinine was significantly increased (35.48, 77.42%) inT1 and T2 group rats and serum urea was also increased in treated animals contrasted with the control group. The results unveiled that MSG at a low dose may causes an adverse outcomes on the hepatic and renal functions.

The relationship between retinal cone density and cortical magnification in human albinism.

The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high density of cone photoreceptors in the fovea and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space—the latter describing cortical magnification (CM)—steadily decrease with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are decreased, but seem to be within normal limits in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure CM in the primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied among individuals with albinism than previously appreciated. Additionally, CM outside the fovea is similar to that in controls, but also more variable. CM in albinism and controls exceeds that which might be predicted based on cone density alone, but is more accurately predicted by retinal ganglion cell density. This finding suggests that decreased foveal cone density in albinism may be partially counteracted by nonuniform connectivity between cones and their downstream signaling partners. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in albinism.

Novel Brown Coat Color (Cocoa) in French Bulldogs Results from a Nonsense Variant in HPS3.

Brown or chocolate coat color in many mammalian species is frequently due to variants at the B locus or TYRP1 gene. In dogs, five different TYRP1 loss-of-function alleles have been described, which explain the vast majority of dogs with brown coat color. Recently, breeders and genetic testing laboratories identified brown French Bulldogs that did not carry any of the known mutant TYRP1 alleles. We sequenced the genome of a TYRP1+/+ brown French Bulldog and compared the data to 655 other canine genomes. A search for private variants revealed a nonsense variant in HPS3, c.2420G>A or p.(Trp807*). The brown dog was homozygous for the mutant allele at this variant. The HPS3 gene encodes a protein required for the correct biogenesis of lysosome-related organelles, including melanosomes. Variants in the human HPS3 gene cause Hermansky–Pudlak syndrome 3, which involves a mild form of oculocutaneous albinism and prolonged bleeding time. A variant in the murine Hps3 gene causes brown coat color in the cocoa mouse mutant. We genotyped a cohort of 373 French Bulldogs and found a strong association of the homozygous mutant HPS3 genotype with the brown coat color. The genotype–phenotype association and the comprehensive knowledge on HPS3 function from other species strongly suggests that HPS3:c.2420G>A is the causative variant for the observed brown coat color in French Bulldogs. In order to clearly distinguish HPS3-related from the TYRP1-related brown coat color, and in line with the murine nomenclature, we propose to designate this dog phenotype as “cocoa”, and the mutant allele as HPS3co.