Table 8

Phenotype Modules and Feline Disorders

Modules

Phenotypes

Disorders


Cardiac

8 genes

-Ras association (RalGDS/AF-6) domain family member 1

(cardiac hypertrophy [58,59])

-solute carrier family 22 (organic cation/carnitine transporter), member 5

(primary carnitine deficiency [75])

-cysteine-rich, angiogenic inducer, 61

(prostate cancer [76])

-tropomodulin 1

-transmembrane protein 38A

-eukaryotic translation initiation factor 2-alpha kinase 1

-snail homolog 1 (Drosophila)

(colon cancer [47])

-interleukin 1 receptor antagonist

(coronary artery disease [77], autoinflammatory disease [54])

-cardiac hypertrophy

-dilated dorsal aorta

-abnormal mitral valve morphology

-abnormal cardiac output

-abnormal myocardial fiber physiology

-enlarged heart

-abnormal outflow tract

-abnormal coronary artery morphology

-mitral valve dysplasia

-tricuspid valve dysplasia

-ventricular septal defects

-atrial septal defects

-dynamic subaortic stenosis

-hypertrophic cardiomyopathy

-restrictive cardiomyopathy

-unclassified cardiomyopathy


Development

7 genes

-TGFB-induced factor homeobox 2

-thioredoxin

(Alzheimer's disease [78])

-E binding protein 1

-potassium inwardly-rectifying channel, subfamily J, member 1

(Andersen-Tawil syndrome [79], short QT syndrome [80])

-retinol dehydrogenase 12 (all-trans/9-cis/11-cis)

(Leber's congenital amaurosis [81])

-arginine vasopressin receptor 1A

-peptidylprolyl cis/trans isomerase, NIMA-interacting 1

(Alzheimer's disease [82])

-abnormal mesoderm development

-abnormal proximal/distal developmental patterning

-abnormal rostral/caudal developmental patterning

-embryonic growth arrest

-abnormal trophoblast layer morphology

-abnormal white adipose tissue

-decreased renal glomerular filtration rate

-decreased cholesterol levels

-decreased triglycerides,

-abnormal intestine morphology

-post natal growth retardation

-retinal neuronal layer morphology

-abnormal retinal apoptosis

-abnormal circulating corticosterone level

-abnormal adrenal gland morphology

-decreased primordial germ cell number

-seminiferous tubule degeneration

-tubular disease

-chronic kidney disease

-amyloidosis

-membranous glomerulopathies

-polycystic kidney disease


Immune and Hematopoietic

9 Genes

-tumor protein D52-like 2

(childhood leukemia [83])

-fragile histidine triad gene

(breast cancer [50], inflammatory bowel disease [84])

-tetraspanin 33

-beclin 1, autophagy related

(Alzheimer's disease [51], colorectal cancer [56], glioblastoma multiforme [55])

-uracil-DNA glycosylase

(hyper-IgM syndrome [57])

-solute carrier family 35, member C1

(leukocyte adhesion deficiency II [85])

-linker for activation of T cell

-bridging integrator 3

-interleukin 1 receptor antagonist

(coronary artery disease [77], autoinflammatory disease [54])

-abnormal macrophage physiology

-abnormal hematopoiesis

-abnormal T-cell proliferation

-abnormal B-cell proliferation

-increased susceptibility to infection

-decreased granulocyte number

-abnormal erythrocyte morphology

-decreased hematocrit

-decreased platelet number

-abnormal immune system biology

-increased spleen germinal cell number

-increased spleen germinal size

-abnormal class switch recombination

-abnormal somatic hypermutation frequency

-lymphoid hyperplasia

-abnormal lymph node primary follicle

-abnormal leukocyte adhesion

-abnormal cytokine secretion

-abnormal interferon secretion

-increased IgE levels

-increased IgG1 levels

-increased IgM levels

- increased interferon gamma secretion

- increased interleukin 10 secretion

- increased interleukin 4 secretion

- enlarged spleen

- liver inflammation

- abnormal chemokine secretion

- abnormal macrophage recruitment

- increased susceptibility to endotoxin shock

- chronic inflammation,

- increased interleukin 1beta secretion

- increased interleukin 17 secretion

- increased interleukin 6 secretion

-Heinz bodies

-pyruvate kinase deficiency

-porphyria

-lymphocytic cholangitis

-neutrophilic cholangitis


Energy, Nutrition and Homeostasis

6 Genes

-phosphatidylserine synthase 2

-glycerol kinase 2

-NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18 kDa (NADH-coenzyme Q reductase)

(Leigh syndrome [49])

-NAD(P)H dehydrogenase, quinone 1

(childhood acute lymphoblastic leukemia [41])

-solute carrier family 22 (organic cation/carnitine transporter), member 5

(primary carnitine deficiency [75])-syntaxin 4

-abnormal phospholipid level

-increased circulating follicle stimulating hormone

-decreased circulating glucose level

-increased fatty acid level

-abnormal body weight

-decreased body temperature

-decreased oxygen consumption

-abnormal gluconeogenesis

-abnormal liver morphology

-decreased circulating glucose

-increased glucagon

-insulin resistance

-abnormal glucose homeostasis

-decreased circulating carnitine

-hypoglycemia

-increased circulating ammonia level

-impaired glucose tolerance

-insulin resistance

-increased circulating insulin level

-insulin resistance

-type II diabetes melitus Congts


Tumorigenesis

5 Genes

-uracil-DNA glycosylase

(hyper-IgM syndrome [57])

-caspase 9, apoptosis-related

(colon cancer [42], inflammatory bowel disease [43])

-cysteine peptidase

-bridging integrator 3

-beclin 1

(Alzheimer's disease [51], colorectal cancer [56], glioblastoma multiforme [55])

-Ras association (RalGDS/AF-6) domain family member 1

(cardiac hypertrophy [58,59])

-B-cell derived lymphoma

-increased sensitivity to oxidative stress

-increased apoptosis

-decreased cellular sensitivity to gamma irradiation

-increased incidence of ionizing radiation induced tumors

-increased tumor incidence

-malignant tumors

-adenocarcinoma

-B-cell lymphoma

-T-cell lymphoma

-cutaneous mast cell tumors

-visceral mast cell tumors

-feline injection site sarcomas

-squamous cell carcinoma

-mammary gland tumors

-meningioma


Sensory

5 Genes

-bridging integrator 3

-mal, T-cell differentiation protein

(protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis [45])

-NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18 kDa (NADH-coenzyme Q reductase)

(Leigh syndrome [49])

-caspase 9, apoptosis-related cysteine peptidase

(colon cancer [42], inflammatory bowel disease [43])

-snail homolog 1(Drosophila)

(colon cancer [47])

-abnormal lens fiber morphology

-cataracts

-abnormal optic nerve nerve morphology

-abnormal eye electrophysiology

-hyperkplexia

-abnormal vision

-blindness

-optic nerve atrophy

-decreased startle response

-abnormal olfactory epithelium morphology

- abnormal Meckel's cartilage morphology

-retinal degeneration

-cataracts


Behavior, Neurological and Nervous System

12 Genes

-N-ethylmaleimide-sensitive factor attachment protein, alpha

-carbohydrate sulfotransferase 10

(melanoma [86])

-transmembrane protein 176B

-solute carrier family 35, member C1

(leukocyte adhesion deficiency II [85])

-glycerol kinase 2

-NAD(P)H dehydrogenase, quinone 2

(Alzheimer's disease [87])

-NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18 kDa (NADH-coenzyme Q reductase)

(Leigh syndrome [49])

-diablo homolog

(progressive hearing loss [88], breast cancer [89])

-caspase 9, apoptosis-related cysteine peptidase

(colon cancer [42], inflammatory bowel disease [43])

-RAB3B, member RAS oncogene family

-snail homolog 1(Drosophila)

(colon cancer [47])

-mal, T-cell differentiation protein

(protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis [45])

-abnormal motor coordination

-impaired balance

-impaired righting response

-abnormal learning and memory

-abnormal spatial learning, ataxia

-abnormal maternal nurturing

-abnormal posture

-abnormal suckling behavior

-hypoactivity

-abnormal motor learning

-abnormal spatial learning

-abnormal spatial working memory

-abnormal emotion and affect

-abnormal gate

-abnormal motor control

-abnormal balance

-abnormal vocalization

-impaired coordination

-abnormal nest building

-abnormal stationary movement

-abnormal CNS synaptic transmission

-reduced long term potentiation

-abnormal excitatory post synaptic potential

-abnormal brain commissure morphology

-abnormal brain development

-abnormal embryonic neuroepithelium layer differentiation

-decreased neuron apoptosis

-decreased neurotransmitter release

-enhanced paired-pulse facilitation

-open neural tube

-abnormal cerebellar granuale layer

-abnormal Purkinje cell layer, small cerebellum

-abnormal brain ventricle morphology

-abnormal cerbral cortex morphology

- abnormal forebrain morphology

-abnormal hindbrain

-abnormal myelination

-abnormal neuron morphology

-abnormal neuron physiology

-astrocytosis, brain vacuoles

-brainstem hemorrhage

-gliosis

-intercranial hemorrage

-lysosomal storage diseases -idiopathic vestibular disease

-congenital unilateral vestibular disease


Mouse orthologs of feline cDNA sequences were used to identify phenotypes from the Mouse Genome Database. 38 genes were selected to represent seven phenotype modules. These genes were associated with a total of 136 phenotypes. Each of the seven modules is listed in the left column. The set of phenotypes associated with the genes in each module are indicated in the middle column. The clinically relevant feline disorders and diseases are listed in the third column. Gene names are listed in the left column. Specific human diseases that each gene is associated with are indicated in parentheses following the gene name and were identified by literature searches.

Irizarry et al. BMC Genomics 2012 13:31   doi:10.1186/1471-2164-13-31

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