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Name: Accepted/
suspected 		Hypersensitivity

I, II, III, IV

Autoantibody Notes
Acute disseminated encephalomyelitis (ADEM) Accepted[1]
Addison's disease interferon omega; transglutaminase; aromatic acid carboxylase; GAD; HAI; 17 hydroxylase; 21 hydroxylase
Agammaglobulinemia IGHM; IGLL1: CD79A; CD79B; BLNK; LRRC8A
Alopecia areata Accepted[2][3] T-cells
Amyotrophic Lateral Sclerosis
Ankylosing Spondylitis Accepted[4][5][6] ANCA? CD8; HLA-B27
Antiphospholipid syndrome Accepted[1] anti-cardiolipin;anti pyruvate dehydrogenase; β2 glycoprotein I; phosphatidylserine; anti apoH; Annexin A5 HLA-DR7, HLA-B8, HLA-DR2, HLA-DR3
Antisynthetase syndrome
Atopic allergy I
Atopic dermatitis I
Autoimmune aplastic anemia
Autoimmune cardiomyopathy Accepted
Autoimmune enteropathy
Autoimmune hemolytic anemia Accepted II complement activation
Autoimmune hepatitis Accepted cell-mediated anti-mitochondrial antibodies; ANA; anti-smooth muscle antibodies, LKM-1; soluble liver antigen
Autoimmune inner ear disease Accepted [7]
Autoimmune lymphoproliferative syndrome Accepted TNFRSF6; defective Fas-CD95 apoptosis
Autoimmune peripheral neuropathy Accepted
Autoimmune pancreatitis Accepted ANA; anti-lactoferrin antibodiesanti-carbonic anhydrase antibodies; rheumatoid factor
Autoimmune polyendocrine syndrome Accepted Unknown or multiple APS-1 see Addison's disease
Autoimmune progesterone dermatitis Accepted
Autoimmune thrombocytopenic purpura Accepted anti gpIIb-IIIa or 1b-IX
Autoimmune urticaria Accepted [8]
Autoimmune uveitis Accepted HLAB-27?
Balo disease/Balo concentric sclerosis
Behçet's disease immune-mediated systemic vasculitis; linkage to HLA-B51 (HLA-B27); very different manifestations with ulcers as common symptom; also called Morbus Adamandiades-Behçet
Berger's disease IgA (elevated in 50% of patients), IgA (in mesangial deposits on kidney biopsy)
Bickerstaff's encephalitis Anti-GQ1b 2/3 patients similar to Guillain-Barré syndrome
Blau syndrome overlaps both sarcoidosis and granuloma annulare
Bullous pemphigoid IgG autoantibodies targeting the type XVII collagen component of hemidesmosomes [9]
Cancer
Castleman's disease Over expression of IL-6
Celiac disease Accepted[10][11][12] IV?? Anti-tissue transglutaminase antibodies HLA-DQ8 and DQ2.5
Chagas disease Suspected[13]
Chronic inflammatory demyelinating polyneuropathy Anti-ganglioside antibodies:anti-GM1, anti-GD1a, anti-GQ1b similar to Guillain-Barré syndrome
Chronic recurrent multifocal osteomyelitis LPIN2, D18S60,similar to Majeed syndrome
Chronic obstructive pulmonary disease Suspected[14][15]
Churg-Strauss syndrome p-ANCA
Cicatricial pemphigoid anti-BP-1, anti BP-2 precipitates C3
Cogan syndrome
Cold agglutinin disease Accepted II IgM idiopathic or secondary to leukemia or infection
Complement component 2 deficiency
Contact dermatitis III
Cranial arteritis aka Temporal arteritis; involves giant cells
CREST syndrome Anti-centromere antibodies Anti-nuclear antibodies
Crohn's disease (one of two types of idiopathic inflammatory bowel disease "IBD") Accepted[1] IV Innate immunity; Th17; Th1; ATG16L1; CARD15;XBP1;
Cushing's Syndrome cortisol binding globulin?
Cutaneous leukocytoclastic angiitis neutrophils
Dego's disease Vasculopathy
Dercum's disease Suspected Lipoid tissue.[16]
Dermatitis herpetiformis IgA; anti-epidermal transglutaminase antibodies
Dermatomyositis Accepted[17] histidine-tRNA anti-signal_recognition_peptide Anti-Mi-2 Anti-Jo1.[18] B- and T-cell perivascular inflammatory infiltrate on muscle biopsy
Diabetes mellitus type 1 Accepted[1] IV Glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated autoantibodies (IA-2), anti-insulin antibodies
Diffuse cutaneous systemic sclerosis anti-nuclear antibodies, anti-centromere and anti-scl70/anti-topoisomerase antibodies[19] COL1A2 and TGF-β1
Dressler's syndrome myocardial neo-antigens formed as a result of the MI
Drug-induced lupus anti-histone
Discoid lupus erythematosus III IL-2 and IFN-gamma>[20]
Eczema LEKTI, SPINK5,[21] filaggrin.,[22] Brain-derived neurotrophic factor (BDNF) and Substance P.[23]
Endometriosis Suspected[24]
Enthesitis-related arthritis[25] . MMP3[26] TRLR2, TLR4,[27] ERAP1[28]
Eosinophilic fasciitis Accepted
Eosinophilic gastroenteritis IgE IL-3, IL-5, GM-CSF, eotaxin
Epidermolysis bullosa acquisita COL7A1
Erythema nodosum
Erythroblastosis fetalis II ABO, Rh, Kell antibodies mother's immune system attacks fetus
Essential mixed cryoglobulinemia
Evan's syndrome
Fibrodysplasia ossificans progressiva ACVR1 Lymphocytes express increased BMP4
Fibrosing alveolitis (or Idiopathic pulmonary fibrosis) SFTPA1, SFTPA2, TERT, and TERC.[29]
Gastritis serum antiparietal and anti-IF antibodies
Gastrointestinal pemphigoid Accepted
Giant cell arteritis macrophage giant cells
Glomerulonephritis Sometimes IgA see Buerger's disease for IgA; Membranous glomerulonephritis for IgG; Membranoproliferative/mesangiocapillary GN (Complement activation); Goodpasture's syndrome; Wegener's granulomatosis
Goodpasture's syndrome Accepted[1] II Anti-Basement Membrane Collagen Type IV Protein
Graves' disease Accepted[1] II thyroid autoantibodies (TSHR-Ab) that activate the TSH-receptor (TSHR)
Guillain-Barré syndrome (GBS) Accepted[1] IV Anti-ganglioside
Hashimoto's encephalopathy Accepted[1] IV alpha-enolase[30]
Hashimoto's thyroiditis Accepted[1] IV antibodies against thyroid peroxidase and/or thyroglobulin HLADR5, CTLA-4
Henoch-Schonlein purpura immunoglobulin A (IgA) and complement component 3 (C3)
Herpes gestationis aka Gestational Pemphigoid IgG and C3 misdirected antibodies intended to protect the placenta
Hidradenitis suppurativa Suspected[31]
Hughes-Stovin syndrome
Hypogammaglobulinemia IGHM, IGLL1, CD79A, BLNK, LRRC8A, CD79B
Idiopathic inflammatory demyelinating diseases a variant of multiple sclerosis
Idiopathic pulmonary fibrosis SFTPA1, SFTPA2, TERT, and TERC.[29]
Idiopathic thrombocytopenic purpura (See Autoimmune thrombocytopenic purpura) Accepted[1] II glycoproteins IIb-IIIa or Ib-IX, immunoglobulin G
IgA nephropathy III? IgA produced from marrow rather than MALT
Inclusion body myositis similar to polymyositis but does not respond to steroid therapy-activated T8 cells
Chronic inflammatory demyelinating polyneuropathy anti-ganglioside antibodies similar to Guillain–Barré syndrome
Interstitial cystitis Suspected[32] Mast cells
Juvenile idiopathic arthritis aka Juvenile rheumatoid arthritis inconsistent ANA Rheumatoid_factor
Kawasaki's disease Suspected ITPKC HLA-B51
Lambert-Eaton myasthenic syndrome voltage-gated calcium channels; Q-type_calcium_channel, synaptogagmin, muscarinic acetylcholine receptor M1 HLA-DR3-B8
Leukocytoclastic vasculitis
Lichen planus
Lichen sclerosus
Linear IgA disease (LAD)
Lou Gehrig's disease (Also Amyotrophic lateral sclerosis) VCP, ATXN2, OPTN, FIG4, TARDBP, ANG, VAPB, FUS, SETX, ALS2, SOD1
Lupoid hepatitis aka Autoimmune_hepatitis ANA and SMA,[33] LKM-1 , LKM-2 or LKM-3; antibodies against soluble liver antigen[34][35](anti-SLA, anti-LP) no autoantibodies detected (~20%)[citation needed]
Lupus erythematosus Accepted[1] III Anti-nuclear antibodies[36] anti-Ro.[37] Also, they are often present in Sjögren's syndrome.[38][39]
Majeed syndrome LPIN2
Ménière's disease III? major peripheral myelin protein P0[40]
Microscopic polyangiitis p-ANCA myeloperoxidase binds to neutrophils causing them to degranulate and damages endothelium
Miller-Fisher syndrome see Guillain-Barre_Syndrome Accepted anti-GQ1b
Mixed connective tissue disease Accepted[1] anti-nuclear antibody anti-U1-RNP HLA-DR4
Morphea Suspected[41]
Mucha-Habermann disease aka Pityriasis_lichenoides_et_varioliformis_acuta T-cells
Multiple sclerosis Suspected IV PECAM-1[42] Anti-Myelin Basic Protein
Myasthenia gravis Accepted[1] II nicotinic_acetylcholine_receptor MuSK_protein HA-B8 HLA-DR3 HLA-DR1
Myositis see Dermatomyositis and Polymyositis see Inclusion-body-myositis
Narcolepsy[43][44] Suspected[45] II? hypocretin or orexin[46] HLA-DQB1*0602[47]
Neuromyelitis optica (also Devic's disease) II? NMO-IgG aquaporin 4.[48][49]
Neuromyotonia Suspected[50] II? voltage-gated potassium channels.[50]
Occular cicatricial pemphigoid II? BP-1, BP-2 C3 deposition
Opsoclonus myoclonus syndrome Suspected IV? Lymphocyte recruitment to CSF[51]
Ord's thyroiditis
Palindromic rheumatism anti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA)[52]
PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus) Suspected II? antibodies against streptococcal infection serve as auto-antibodies
Paraneoplastic cerebellar degeneration IV?[53] II? anti-Yo[54] (anti-cdr-2[55] in purkinje fibers) anti-Hu, anti-Tr, antiglutamate receptor
Paroxysmal nocturnal hemoglobinuria (PNH) Sometimes(?) complement attacks RBCs
Parry Romberg syndrome ANA
Parsonage-Turner syndrome
Pars planitis
Pemphigus vulgaris Accepted[1] II Anti-Desmoglein 3
Pernicious anaemia Accepted[56] II anti-parietal cell antibody
Perivenous encephalomyelitis
POEMS syndrome interleukin 1β, interleukin 6 and TNFα. vascular endothelial growth factor (VEGF), given the .[57]
Polyarteritis nodosa
Polymyalgia rheumatica
Polymyositis Accepted[17] IFN-gamma, IL-1, TNF-alpha
Primary biliary cirrhosis Accepted[58] Anti-p62, Anti-sp100, Anti-Mitochondrial(M2)Anti-Ro aka SSA.[37] Also, they are often present in Sjögren's syndrome.[38][39]
Primary sclerosing cholangitis overlap with primary biliary cirrhosis?
Progressive inflammatory neuropathy Suspected
Psoriasis Accepted[59] IV? CD-8 T-cells, HLA-Cw6, IL-12b, IL-23b, TNFalpha, nfKb
Psoriatic arthritis Accepted[60] IV? HLA=B27
Pyoderma gangrenosum Can occur in conjunction with other immune-related disorders
Pure red cell aplasia
Rasmussen's encephalitis anti-NR2A antibodies
Raynaud phenomenon Suspected Can occur in conjunction with other immune-related disorders
Relapsing polychondritis Accepted[61]
Reiter's syndrome
Restless leg syndrome Suspected May occur in Sjögren's syndrome, celiac disease, and rheumatoid arthritis or in derangements of iron metabolism
Retroperitoneal fibrosis
Rheumatoid arthritis Accepted[1] III Rheumatoid factor (anti-IgGFc), Anti-MCV , ACPAs(Vimentin HLA-DR4, PTPN22, depleted B cells, TNF alpha, IL-17, (also maybe IL-1, 6, and 15)
Rheumatic_fever II streptococcal M protein cross reacts with human myosin,[62] anti-DNase B, ASO
Sarcoidosis Suspected IV[63][64] BTNL2; HLA-B7-DR15; HLA DR3-DQ2.[65]
Schizophrenia Suspected[66][67][68]
Schmidt syndrome another form of APS anti-21 hydroxylase, anti-17 hydroxylase[69] DQ2, DQ8 and DRB1*0404
Schnitzler syndrome IgM?
Scleritis
Scleroderma Suspected[41] IV? Scl-70 Anti-topoisomerase dysregulated apoptosis?
Serum Sickness III
Sjögren's syndrome Accepted[1] Anti-ro.[37] Also, they are often present in Sjögren's syndrome.[38][39]
Spondyloarthropathy HLA-B27
Still's disease see Juvenile Rheumatoid Arthritis ANA macrophage migration inhibitory factor[70]
Stiff person syndrome Suspected glutamic acid decarboxylase (GAD),[71] GLRA1 (glycine receptor
Subacute bacterial endocarditis (SBE) III [72] essential mixed cryoglobulinemia
Susac's syndrome
Sweet's syndrome GCSF
Sydenham chorea see PANDAS
Sympathetic ophthalmia ocular antigens following trauma
Systemic lupus erythematosis see Lupus erythematosis III
Takayasu's arteritis
Temporal arteritis (also known as "giant cell arteritis") Accepted[1] IV
Thrombocytopenia II glycoproteins IIb-IIIa or Ib-IX in ITP anti-ADAMTS13 in TTP.[73] and HUS anti-cardiolipin (anti-cardiolipin antibodies) and β2 glycoprotein I in Antiphospholipid syndrome anti-HPA-1a, anti-HPA-5b, and others[74] in NAIT multiple mechanisms
Tolosa-Hunt syndrome
Transverse myelitis Accepted Transverse Myelitis is a rare neurological disorder that is part of a spectrum of neuroimmunologic diseases of the central nervous system. http://www.myelitis.org/
Ulcerative colitis (one of two types of idiopathic inflammatory bowel disease "IBD") Accepted[1] IV
Undifferentiated connective tissue disease different from Mixed connective tissue disease Accepted anti-nuclear antibody HLA-DR4
Undifferentiated spondyloarthropathy
Urticarial vasculitis II? anti C1q antibodies[75] clinically may resemble type I hypersensitivity!
Vasculitis Accepted[9] III sometimes ANCA
Vitiligo Suspected[76][77] NALP-1 RERE, PTPN22, LPP, IL2RA, GZMB, UBASH3A and C1QTNF6
Wegener's granulomatosis Accepted[78] Anti-neutrophil cytoplasmic(cANCA)

Getting closer to new algorithm

[edit]

The following is highly speculative and lists few if any references. It is probably more appropriate for a User page, but I dont get much traffic here anyway, so please don't delete anything without letting me know. The lists are generated from Smith's. [79]

Developmental Disorders

[edit]

As multicellular creatures evolved from an ancient yeast-like ancestor (with approximately 6,000 genes), genes were duplicated as a major mechanism of evolution. Twice whole genomes were duplicated in the animal line (yielding roughly 24,000 genes in higher animals). This process is still seen frequently in large-species plant variants. It seems likely that at some points in evolution it might be necessary to silence duplicated genes, after which they undergo apparently random mutations until they have adapated to a new function. It seems increasingly apparent that this may not be a completely random process, and it is unclear by which mechanisms this seemingly "guided selection" may occur. It is possible that untranslated RNA may play a much more active role than was previously thought. It is important to recognize that with increasingly complex genomes, the mechanisms of evolution may seem to reach a point of diminishing returns, wherein the complexities of gene expression constrain evolution to relatively minor mutations; whole genome duplications do not appear to be well tolerated in higher animals.

An appreciation of the mechanisms of evolution should enable students to understand how the genome works, how evolution proceeds, and how "attempted evolution" may result in conditions of reduced function (developmental disability) and perhaps offer insight as to the possibility of an improved genome. It is the opinion of this author that it is unwise to "tinker" with these mechanism before they are more fully understood because of the possibilities of inadvertently triggering malignant transformation in the individual, and of generating voracious super-viruses that could potentially affect all life on earth. We must proceed with caution.

If the hypothesis is true that we eukaryotes basically evolved from a simpler yeast-like organism (maybe with 6,000 genes or so), then it's possible that a list of essential housekeeping genes may yield a picture of what this simpler genome may have looked like. Later as genes were duplicated and adapted for other functions, the manner in which they are subsequently expressed might be deduced from knowledge of the ancestral gene. For example, it appears that cytoskeletal elements essential for mitosis (tubulin, actin, etc) appear to have been adapted in specialized tissues (ie:musculo-skeletal tissues). Although this over-simplified view may not be entirely accurate (there are likely many more mechanisms of evolution at play) such an approach may a useful didactic structure that could at least aid the student in memorization.

Housekeeping genes

[edit]

Among the limitations in compiling such a list of housekeeping genes, many assumptions are drawn which may not be entirely correct. For example, attempts have been made to use such genes as internal standards for gene expression under the assumption that housekeeping genes will not vary in concentration throughout a cell cycle. This proves to be not entirely true. Another limitation is the fact that many techniques used to determine gene expression are based on measurements of mRNA....which in reality may or may not be translated. Transcription alone does not equal expression. Finally the usage of short tags to hybridize with mRNA may misidentify closely-related genes. When such divergant genes may be named by completely different naming schemes, the ancestral link between them may be completely inapparent. Naming conventions based on structure might do a lot to minimize this confusion and thus easier to draw parallels between homologous genes.

When mutations occur in such housekeeping genes, it is likely that the changes in an individual will be profound. Sly syndrome, a mutation in GUSB, Sanfilippo syndrome a mutation in SHSH, Rendu-Osler-Weber syndrome a mutation in ACVRL1, and Alagille syndrome a mutation in JAG1 are examples of mutations in such housekeeping genes that can have profound effects on the individual. It seems likely that small mutations in highly conserved housekeeping genes may be lethal. Describing the phenotype of an individual in whom every cell is likely to be abnormal can be a challenging task. Conversely pinning down one defective gene in an individual with so many abnormalities can be equally challenging. Previous efforts at syndrome identification have yielded limited success. Alternatively a gene that is expressed in only one tissues such as Hemoglobin B mutated to Hemoglobin S, can have secondary effects in other tissues (ie: frontal bossing of the cranium although the gene is not directly expressed in cranial tissue.) There are definite limitations in using phenotype to categorically determine genotype; yet prior to the technical advances of the 21st century, comparisons of phenotype were among the only effective tools available to clinicians.

Other profound genes

[edit]

Body patterning genes

[edit]

The axes of the multicellular organism are laid out extremely early. In the case of drosophila, in which nuclei divide without actual cell division (resulting in giant multinucleated cells or syncytia) the body patterning is accomplished with cytosolic gradiants. Although this may represent a divergent pattern from the pattern seen in vertebrates, it is notable that many of the same gene products effect similar body patterning in both ancestries. Homeobox genes (the very structure of which denote a common "homeobox" which implies a shared ancestry among the genes) accomplish the basic body pattern formation. As these genes were themselves duplicated and underwent divergent evolution, they came to pattern other body parts.

  • MID1 Midline structures Opitz syndrome (aka TRIM18)

Facial genes

[edit]

As multicellular organisms develop, eventually their arose the phenomenon of a "head" region. Whether for the purposes of navigation or ingestion, it seems that at least ontologically rostral elements form first.

Cartilage genes

[edit]

The intimate relationship between cartilage/bone/and facial formation often results in cartilage defects manifesting themselves in a particular facial appearance, together with skeletal malformation.

Mucopolysaccharidosis

[edit]

Sometimes referred to as "storage" diseases, there is a deficiency in the enzymes involved in the synthesis of proteoglycans that are major ingredients of cartilage. While the pathology results in course facial features, skeletal dysplasia, short stature, mental retardation and corneal clouding. One of the microscopic findings is an increase of upstream metabolites which get "backed up" in lysosomes.

Mucolipidosis

[edit]
  • NEU1 Sialidosis Mucolipidosis I lysosomal sialidase
  • GNPTAB Mucolipidosis II and III Pseudo-Hurler n-acetyl-glucosamine phosphate transferase
  • GNPTG Mucolipidosis III gamma

Collagen

[edit]

Cranial genes

[edit]

The first osseous structure to emerge (after teeth) were probably analagous to skull and/or exoskeletal development. This is likely to have occurred before the divergence of vertebrates and invertebrates. Whether membranous bone formation is truly homologous to exoskeletal structures is highly speculative. Furthermore it is crucial to note the intimate relationship between underlying brain formation and overlying bone formation. This is particularly evident in the craniosynostosis syndromes.

Primary Craniosynostosis

[edit]
  • RUNX2 Cleidocranial dysostosis.
  • ANKH Craniometaphyseal Dysplasia
  • FGFR1 Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome
  • FGFR2 Apert syndrome, Antley-Bixler syndrome Pfeiffer syndrome ,Crouzon syndrome , Jackson-Weiss syndrome
  • FGFR3 achondroplasia/hypochondroplasia , thanatophoric dwarfism
  • FGFR10 Baller-Gerald SyndromeCite error: The <ref> tag has too many names (see the help page). Lacrimo-Auriculo-Dento-Digital SyndromeCite error: The <ref> tag has too many names (see the help page).
  • TWIST Saethre-Chotzen syndrome
  • POR P-450 Oxidoreductase deficiency; Williams syndrome ormixed function oxidase deficiency

Secondary Craniosynostosis

[edit]

By definition secondary craniosynostosis occurs because of a defect in the development of the underlying brain. Therefore, these genes might be considered just as relevant in the subsequent section on "Brain genes."

  • HSP90AB1 On this list because of Smith's, but not sure it belongs. Formerly HSPC2 it looks more like a constitutive gene that is sometime upregulated in brain tumors. Chaperonin
  • DMPK Dystrophia Myotonica Myotonic dystrophy formerly DM1 Not sure about this one either!
  • PEX?
  • COH1 Cohen syndrome
  • GLI3 Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B

Brain genes

[edit]

The formation of neural tissue is eerily similar to the formation of bone. In both tissues, a cartilaginous anlage (notochord vs. limb anlage) is laid down. In both tissues a more specialized cell (neural crest cells vs. osteoblasts) interacts with the cartilage and is positioned by it. Further differentiation of brain tissue (such as certain FOX genes) demonstrate a pattern of gene duplication, resulting in further branching or layering of neural structures.

Musculoskeletal genes

[edit]

While bone tissue is modeled on cartilaginous anlage, muscle tissue appears to upregulate cytoskeletal elements as it differentiates into muscules. There is also intimate interaction with neural tissue. There is also resurrection of syncytial development.


Limb defects

[edit]

Although the purpose of Smith's is to identify "recognizable" patterns, it appears that genes that are responsible for limb formation are frequently so ancient that they are also coapted in other processes. For example; in ulnar-mammary syndrome, while the ulna is a very ancient anatomic structure emerging long before mammals, the gene appears to have been coapted in a very different process in the development of mammary glands. TAR syndrome is another example in which efforts have been made to find a single gene to expain the divergent effects within a syndrome. However efforts to implicate TPO and several HOX genes have been unsuccessful. This may represent a case of contiguous genes (or even genes that share a similar promoter) that are simply deleted/altered together (simple gene linkage). Thus it becomes difficult to interpret some of these syndromes.

Overgrowth Syndromes

[edit]

Muscle/Cardiac genes

[edit]

Digestive genes

[edit]

Excretory genes

[edit]

In some cases the same gene (or a recent copy thereof) is used for ion channelling as in cardiac/muscle tissue.

References

[edit]
  1. ^ a b c d e f g h i j k l m n o p q r Autoimmune+Diseases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  2. ^ American Academy of Dermatology, http://www.aad.org/public/publications/pamphlets/common_alopecia.html
  3. ^ htmlThe University of Texas MD Anderson Cancer Center, http://www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-types/alopecia-areata/index.html
  4. ^ HLA-B27 and Ankylosing Spondylitis, http://www.hlab27.com
  5. ^ Inflammatory Diseases of Immune Dysregulation, http://www.idid.us
  6. ^ Khan MA, Khan MK (1982). "Diagnostic Value of HLA-B27 Testing in Ankylosing Spondylitis and Reiter's Syndrome". Annals of Internal Medicine January 1, 1982 Vol. 96 No. 1 70-76. 96 (1): 70–76, author reply 76. doi:10.7326/0003-4819-96-1-70. PMID 7053711.
  7. ^ "Autoimmune Inner Ear Disease, Baylor College of Medicine". 1993.
  8. ^ Soundararajan S, Kikuchi Y, Kusumam J, Kaplan AP (2004). "Functional | assessment of pathogenic IgG subclass in chronic autoimmune urticaria". Journal of Allergy and Clinical. 115 (4): 815–21. doi:10.1016/j.jaci.2004.12.1120. PMID 15806004. {{cite journal}}: Unknown parameter |unused_data= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ a b "Autoimmune Disorders: Immune Disorders: Merck Manual Home Health Handbook".
  10. ^ "Celiac Disease".
  11. ^ Meize-Grochowski R (2005). "Celiac disease: a multisystem autoimmune disorder". Gastroenterol Nurs. 28 (5): 394–402, quiz 403–4. doi:10.1097/00001610-200509000-00005. PMID 16234635. S2CID 44364035.
  12. ^ Sollid LM, Jabri B (2005). "Is celiac disease an autoimmune disorder?". Curr. Opin. Immunol. 17 (6): 595–600. doi:10.1016/j.coi.2005.09.015. PMID 16214317. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ Hyland KV, Engman DM (2006). "Further thoughts on where we stand on the autoimmunity hypothesis of Chagas disease". Trends Parasitol. 22 (3): 101–2, author reply 103. doi:10.1016/j.pt.2006.01.001. PMID 16446117.
  14. ^ Agustí A, MacNee W, Donaldson K, Cosio M. (2003). "Hypothesis: does COPD have an autoimmune component?". Thorax. 58 (10): 832–834. doi:10.1136/thorax.58.10.832. PMC 1746486. PMID 14514931.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Lee SH, Goswami S, Grudo A; et al. (2007). "Antielastin autoimmunity in tobacco smoking-induced emphysema". Nat. Med. 13 (5): 567–9. doi:10.1038/nm1583. PMID 17450149. S2CID 1732877. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  16. ^ Singal A, Janiga JJ, Bossenbroek NM, Lim HW (2007). "Dercum's disease (adiposis dolorosa): a report of improvement with infliximab and methotrexate". J Eur Acad Dermatol Venereol. 21 (5): 070209222700013––. doi:10.1111/j.1468-3083.2006.02021.x. PMID 17448013. S2CID 12981175. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ a b "Polymyositis and Dermatomyositis: Autoimmune Disorders of Connective Tissue: Merck Manual Home Health Handbook".
  18. ^ Ghirardello, A (2006). "Clinical implications of autoantibody screening in patients with autoimmune myositis". Autoimmunity. 39 (3): 217–221. doi:10.1080/08916930600622645. PMID 16769655. S2CID 2411394. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  19. ^ Jimenez SA, Derk CT (2004). "Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis". Ann. Intern. Med. 140 (1): 37–50. doi:10.7326/0003-4819-140-1-200401060-00010. PMID 14706971. S2CID 9610863.
  20. ^ Toro JR, Finlay D, Dou X, Zheng SC, LeBoit PE, Connoly KM. "Detection of Type 1 Cytokines in Discoid Lupus Erythematosus". Annals of Internal Medicine 2000. 136: 1497–1501. PMID 11115160.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Walley AJ, Chavanas S, Moffatt MF; et al. (2001). "Gene polymorphism in Netherton and common atopic disease". Nat. Genet. 29 (2): 175–8. doi:10.1038/ng728. PMID 11544479. S2CID 20292050. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  22. ^ Palmer CN; et al. (2006). "Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis". Nature Genetics. 38 (4): 441–6. doi:10.1038/ng1767. PMID 16550169. S2CID 2500278. {{cite journal}}: Explicit use of et al. in: |author= (help)
  23. ^ "'Blood chemicals link' to eczema -- Scientists have identified two blood chemicals linked to itchy eczema, offering new treatment possibilities". BBC News. 26 August 2007. Retrieved 2007-10-16.
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ANOTHER VERSION=

[edit]

Getting closer to new algorithm

[edit]

The following is highly speculative and lists few if any references. It is probably more appropriate for a User page, but I dont get much traffic here anyway, so please don't delete anything without letting me know. The lists are generated from Smith's. [1]

Developmental Disorders

[edit]

As multicellular creatures evolved from an ancient yeast-like ancestor (with approximately 6,000 genes), genes were duplicated as a major mechanism of evolution. Twice whole genomes were duplicated in the animal line (yielding roughly 24,000 genes in higher animals). This process is still seen frequently in large-species plant variants. It seems likely that at some points in evolution it might be necessary to silence duplicated genes, after which they undergo apparently random mutations until they have adapated to a new function. It seems increasingly apparent that this may not be a completely random process, and it is unclear by which mechanisms this seemingly "guided selection" may occur. It is possible that untranslated RNA may play a much more active role than was previously thought. It is important to recognize that with increasingly complex genomes, the mechanisms of evolution may seem to reach a point of diminishing returns, wherein the complexities of gene expression constrain evolution to relatively minor mutations; whole genome duplications do not appear to be well tolerated in higher animals.

An appreciation of the mechanisms of evolution should enable students to understand how the genome works, how evolution proceeds, and how "attempted evolution" may result in conditions of reduced function (developmental disability) and perhaps offer insight as to the possibility of an improved genome. It is the opinion of this author that it is unwise to "tinker" with these mechanism before they are more fully understood because of the possibilities of inadvertently triggering malignant transformation in the individual, and of generating voracious super-viruses that could potentially affect all life on earth. We must proceed with caution.

If the hypothesis is true that we eukaryotes basically evolved from a simpler yeast-like organism (maybe with 6,000 genes or so), then it's possible that a list of essential housekeeping genes may yield a picture of what this simpler genome may have looked like. Later as genes were duplicated and adapted for other functions, the manner in which they are subsequently expressed might be deduced from knowledge of the ancestral gene. For example, it appears that cytoskeletal elements essential for mitosis (tubulin, actin, etc) appear to have been adapted in specialized tissues (ie:musculo-skeletal tissues). Although this over-simplified view may not be entirely accurate (there are likely many more mechanisms of evolution at play) such an approach may a useful didactic structure that could at least aid the student in memorization.

Housekeeping genes

[edit]

Among the limitations in compiling such a list of housekeeping genes, many assumptions are drawn which may not be entirely correct. For example, attempts have been made to use such genes as internal standards for gene expression under the assumption that housekeeping genes will not vary in concentration throughout a cell cycle. This proves to be not entirely true. Another limitation is the fact that many techniques used to determine gene expression are based on measurements of mRNA....which in reality may or may not be translated. Transcription alone does not equal expression. Finally the usage of short tags to hybridize with mRNA may misidentify closely-related genes. When such divergant genes may be named by completely different naming schemes, the ancestral link between them may be completely inapparent. Naming conventions based on structure might do a lot to minimize this confusion and thus easier to draw parallels between homologous genes.

When mutations occur in such housekeeping genes, it is likely that the changes in an individual will be profound. Sly syndrome, a mutation in GUSB, Sanfilippo syndrome a mutation in SHSH, Rendu-Osler-Weber syndrome a mutation in ACVRL1, and Alagille syndrome a mutation in JAG1 are examples of mutations in such housekeeping genes that can have profound effects on the individual. It seems likely that small mutations in highly conserved housekeeping genes may be lethal. Describing the phenotype of an individual in whom every cell is likely to be abnormal can be a challenging task. Conversely pinning down one defective gene in an individual with so many abnormalities can be equally challenging. Previous efforts at syndrome identification have yielded limited success. Alternatively a gene that is expressed in only one tissues such as Hemoglobin B mutated to Hemoglobin S, can have secondary effects in other tissues (ie: frontal bossing of the cranium although the gene is not directly expressed in cranial tissue.) There are definite limitations in using phenotype to categorically determine genotype; yet prior to the technical advances of the 21st century, comparisons of phenotype were among the only effective tools available to clinicians.

Multicellularity

[edit]

If we interpret "housekeeping genes" to represent the basic cellular constituents that would allow a single-celled eukaroyote to live independently, then the next round of genes that allow for cellular differentiation may expand some functions, but decrease others. The irony of the multicellular organism is that it's individual cells can actually be less complex....possibly allowing for some genes to be turned off. A more refined definition of a housekeeping gene then might be a subset of genes that simply cannot be turned off. And yet, that may mean different genes in different cell types. It might be more useful to think of a "housekeeping niche" rather than a "housekeeping gene." Furthermore, rounds of gene duplication allow an organism to evolve different variations of genes to fill a particular housekeeping "niche" in different cell types. For example, the isoenzymes of lactate-dehydrogenase are expressed differently in cardiac tissue as in other tissues (which enabled physicians to use isoenzyme differentiation as a means to detect cardiac injury.)

Morula

[edit]

Zygote divides into 32 cells; 12 as the inner cell mass (ICM) (destined to become the embryo) and 22 as the tropho....something...the outer cells that become the extra-embryonic protective tissue.

Blastocyst

[edit]

(64 cells?)Trophoblast cells pump fluid from outside to inside, causing a split between the inferior trophoblast layer and the ICM. This new surface (on the underside of the ICM) is called the hypoblast. The cavity that forms is called the blastocyst and is destined to become the yolk sac. Next a similar process occurs between the upper layers of the trophoblast and the upper layers of the ICM creating a cavity that will become the amniotic sac. The upper surface is now called the epiblast.

Gastrulation

[edit]

(18,000 cells? Day 15) The Primitive_Streak establishes what will become the axis of the embryo (us and all our bilaterian cousins (governed by WNT3 (similar to chick WNT8C?) (neg reg: axin, crescent DKK-1) plus Vg1 plus FGF plus BMP(neg reg: chordin)(plus Lef1 and B-catenin in marginal zones). Nodal (neg reg: {Cerberus-like]] and Lefty), chordin, and brachury are also implicated in formation of the primitive streak Cells of the epiblast lose some of their adhesive qualities and slide down a hole that forms on the "tail" end of the axis. As they slip between epiblast (which now becomes epidermal layer) and hypoblast (endoderm), they form the new mesodermal layer.



Genes implied in developmental disorders

[edit]
  • LMNA Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome
  • CSNB?
  • RecQ_helicase Progeria syndromes: Werner syndrome (WS), BLM gene in Bloom syndrome (BS), and RECQ4 in Rhothmund-Thomson's syndrome
  • WRNWerner syndrome (WS)
  • PITX2 Pituitary homeobox 2 Axenfeld-Rieger syndrome (ARS), iridogoniodysgenesis syndrome (IGDS), and sporadic cases of Peters anomaly
  • COL1A1 Ehlers-Danlos, Osteogenesis Imperfecta types 1-4, osteoporosis
  • COL1A2 Ehlers-Danlos, Osteogenesis Imperfecta, and atypical Marfan's Syndrome
  • FBN1 microfibrils Marfan syndrome, isolated ectopia lentis, autosomal dominant Weill-Marchesani syndrome, MASS syndrome, and Shprintzen-Goldberg craniosynostosis
  • FBN2 Beal's Syndrome.

Body patterning genes

[edit]

The axes of the multicellular organism are laid out extremely early. In the case of drosophila, in which nuclei divide without actual cell division (resulting in giant multinucleated cells or syncytia) the body patterning is accomplished with cytosolic gradiants. Although this may represent a divergent pattern from the pattern seen in vertebrates, it is notable that many of the same gene products effect similar body patterning in both ancestries. Homeobox genes (the very structure of which denote a common "homeobox" which implies a shared ancestry among the genes) accomplish the basic body pattern formation. As these genes were themselves duplicated and underwent divergent evolution, they came to pattern other body parts.

Facial genes

[edit]

As multicellular organisms develop, eventually their arose the phenomenon of a "head" region. Whether for the purposes of navigation or ingestion, it seems that at least ontologically rostral elements form first.

Cartilage genes

[edit]

The intimate relationship between cartilage/bone/and facial formation often results in cartilage defects manifesting themselves in a particular facial appearance, together with skeletal malformation.

Cranial genes

[edit]

The first osseous structure to emerge (after teeth) were probably analagous to skull and/or exoskeletal development. This is likely to have occurred before the divergence of vertebrates and invertebrates. Whether membranous bone formation is truly homologous to exoskeletal structures is highly speculative. Furthermore it is crucial to note the intimate relationship between underlying brain formation and overlying bone formation. This is particularly evident in the craniosynostosis syndromes.

Primary Craniosynostosis

[edit]

Secondary Craniosynostosis

[edit]

By definition secondary craniosynostosis occurs because of a defect in the development of the underlying brain. Therefore, these genes might be considered just as relevant in the subsequent section on "Brain genes."

Brain genes

[edit]

The formation of neural tissue is eerily similar to the formation of bone. In both tissues, a cartilaginous anlage (notochord vs. limb anlage) is laid down. In both tissues a more specialized cell (neural crest cells vs. osteoblasts) interacts with the cartilage and is positioned by it. Further differentiation of brain tissue (such as certain FOX genes) demonstrate a pattern of gene duplication, resulting in further branching or layering of neural structures.

Musculoskeletal genes

[edit]

While bone tissue is modeled on cartilaginous anlage, muscle tissue appears to upregulate cytoskeletal elements as it differentiates into muscules. There is also intimate interaction with neural tissue. There is also resurrection of syncytial development.

Limb defects

[edit]

Overgrowth Syndromes

[edit]

Cardiac genes

[edit]

Digestive genes

[edit]

Excretory genes

[edit]

In some cases the same gene (or a recent copy thereof) is used for ion channelling as in cardiac/muscle tissue.

References

[edit]
  1. ^ Kenneth Lyons Jones. (2006). Smiths Recognizable Patterns of Human malformations (sixth ed.).|
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