User:Doctorwolfie/sandbox

Getting closer to new algorithm
''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. ''

=Developmental Disorders= 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
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

 * LMNA familial partial lipodystrophy loss of subcutaneous fat, Emery-Dreifuss muscular dystrophy myopathy and cardiomyopathy, 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
 * TRIM50 Williams syndrome
 * LIMK1 Williams syndrome
 * WRN Werner syndrome (WS)
 * PITX2 Pituitary homeobox 2 Axenfeld-Rieger syndrome (ARS), iridogoniodysgenesis syndrome (IGDS), and sporadic cases of Peters anomaly
 * 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
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
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.
 * PAX3 Waardenburg syndrome type I
 * MITF Microphthalmia associated transcription factor Tietz syndrome and Waardenburg syndrome type IIA
 * CLCN7 Chloride channel 7 (regulated by MITF)
 * WS2B Waardenburg syndrome type IIB
 * WS2C Waardenburg syndrome type IIC
 * SNAI2 Waardenburg syndrome type IID
 * PAX3 Waardenburg syndrome type III
 * EDNRB Waardenberg-Hirschsprung, Waardenburg-Shah (Waardenberg syndrome type IV
 * EDN3 "   "   "   "   "   "   "   "   "   "   "   "
 * SOX10 "  "   "   "   "   "   "   "   "   "   "   "
 * MYOZ3 Myozenin 3
 * IRF6 Interferon regulating factor van der Woude syndrome or popliteal pterygium syndrome
 * EYA1 Homolog of eyeless in drosophila
 * CHD7 ATP dependent chromatin remodeler CHARGE syndrome
 * TCOF1 Treacher Collins syndrome
 * OFD1 Oral-facial-digital syndrome
 * FGD1 Faciogenital dysplasia Aarskog-Scott syndrome
 * LMX1A or B Transcription factor for Insulin

Cartilage genes
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
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.


 * IDUA Hurler syndrome MPS I alpha-L iduronidase
 * IDS Hunter syndrome MPS II Iduronate-2-sulfatase
 * SGSH Sanfilippo syndrome MPS IIIA N-sulphoglucosamine sulphohydrolase
 * NAGLU Sanfilippo syndrome MPS IIIB Alpha-N-acetylglucosaminidase
 * HGSNAT Sanfilippo syndrome MPS IIIC Heparan-alpha-glucosaminide N-acetyltransferase
 * GNSSanfilippo syndrome MPS IIID N-acetylglucosamine-6-sulfatase
 * GALNS Morquio syndrome A MPS IVA N-acetylgalactosamine-6-sulfatase
 * GLB1 Morquio syndrome B MPS IVB β-galactosidase
 * ARSB Maroteaux-Lamy syndrome MPS VI N-acetylgalactosamine-4-sulfatase
 * GUSB Sly syndrome MPSVII β-glucuronidase
 * HYAL1 Natowicz syndrome MPSVI Hyaluronidase
 * EXT1endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Hereditary multiple exostoses
 * EXT2 "
 * EXT3 "

Mucolipidosis

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

Collagen

 * COL1A1 Ehlers-Danlos syndrome, Osteogenesis Imperfecta types 1-4, osteoporosis
 * COL1A2 Ehlers-Danlos syndrome, Osteogenesis Imperfecta, and atypical Marfan's Syndrome
 * COL2A1 achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type
 * SOX9 (regulates COL2A) Campomelic dysplasia
 * COL11A1 Stickler syndrome type II and with Marshall syndrome
 * TRPS1 tricho-rhino-phalangeal syndrome (TRPS) types I-III Langer-Giedion syndrome
 * ATRX X-linked alpha thalassemia mental retardation Transcriptional regulator ATRX contains an ATPase / helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins
 * ROR2 receptor tyrosine kinase-like orphan receptor Robinow syndrome and autosomal dominant brachydactyly B.
 * PHCR7

Cranial genes
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
0270-7306/07/$08.00+0    doi:10.1128/MCB.00544-07 ref/>
 * 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 Syndrome Lacrimo-Auriculo-Dento-Digital Syndrome<ref name= "FGFR10B" Imad Shams,1 Edyta Rohmann,2,3 Veraragavan P. Eswarakumar,1 Erin D. Lew,1 Satoru Yuzawa,1 Bernd Wollnik,2,3 Joseph Schlessinger,1 and Irit Lax1* Lacrimo-Auriculo-Dento-Digital Syndrome Is Caused by Reduced Activity of the Fibroblast Growth Factor 10 (FGF10)-FGF Receptor 2 Signaling Pathway Molecular and Cellular Biology, October 2007, p. 6903-6912, Vol. 27, No. 19
 * TWIST Saethre-Chotzen syndrome
 * POR P-450 Oxidoreductase deficiency; Williams syndrome ormixed function oxidase deficiency

Secondary Craniosynostosis
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
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.


 * GLI3 Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B
 * L1CAM X-linked neurological syndromes known by the acronym CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus)
 * POMT1 ?limb-girdle muscular dystrophy type LGMD2K
 * PAFAH1B1 aka LIS1 Miller-Dieker lissencephaly syndrome
 * ATM ataxia-telangiectasia mutated syndrome interacts with Bloom syndrome protein
 * ATP7A Menke syndrome
 * SNRPN Prader-Willi syndrome
 * UBE3A Angelman syndrome
 * FBN3 Fibrillin 3 Weill-Marchesani syndrome

Musculoskeletal genes
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.
 * SHOX idiopathic short stature (short stature of unknown cause without other symptoms), Léri-Weill dyschondrosteosis, and Langer mesomelic dysplasia.
 * GNAS1 pseudohypoparathyroidism type 1a, pseudohypoparathyroidism type 1b, Albright hereditary osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright syndrome, progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors
 * TRIM37 Mulibrey nanism (also muscle-liver-brain-eye nanism, Perheentupa syndrome, and pericardial constriction with growth failure
 * TCIRG1 Malignant osteopetrosis (osteoclasts fail to differentiate)
 * CLCN7 Chloride channel 7 Albers-Schonberg disease, malignant osteopetrosis
 * SALL1 Townes-Brocks syndrome (TBS) as well as bronchio-oto-renal syndrome (BOR)
 * FLNA X-Linked Periventricular Heterotopia (neuronal migration to the cortex
 * RPS6KA3 Coffin-Lowry syndrome (CLS)
 * COMP????? Multiple epiphyseal displasia, pseudoosteochondral dysplasia
 * COL9A1, 2, 3 Multiple epiphyseal dysplasia
 * COL2A1 achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type
 * SOX9 campomelic dysplasia, frequently with sex reversal
 * DYM two types of recessive osteochondrodysplasia, Dyggve-Melchior-Clausen (DMC) dysplasia and Smith-McCort (SMC) dysplasia, which involve both skeletal defects and mental retardation
 * FLNB boomerang dysplasia and atelosteogenesis type I
 * RMRP cartilage-hair hypoplasia
 * PTHRP BRACHYDACTYLY, TYPE E2
 * SBDS Shwachman-Bodian-Diamond syndrome
 * EBP Conradi-Hünermann syndrome
 * ARSE X-linked recessive chondrodysplasia punctata
 * PEX7 Peroxin 7 Refsum's disease and rhizomelic chondrodysplasia punctata
 * ALPL hypophosphatasia

Limb defects
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.
 * GDF5 acromesomelic dysplasia, Hunter-Thompson type; brachydactyly, type C; and chondrodysplasia, Grebe type
 * TBX3 ulnar-mammary syndrome, affecting limb, apocrine gland, tooth, hair, and genital development
 * TBX5 Holt-Oram syndrome
 * NSDHL Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (also known as "CHILD syndrome") is a genetic disorder with onset at birth seen almost exclusively in females
 * RPS19 Diamond-Blackfan anemia (DBA), a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors, in a subset of patients

Overgrowth Syndromes

 * FBN1 Marfan syndrome, isolated ectopia lentis, autosomal dominant Weill-Marchesani syndrome, MASS syndrome, and Shprintzen-Goldberg craniosynostosis syndrome
 * FMR1 fragile X mental retardation 1
 * NSD1 Sotos syndrome and Weaver syndrome
 * IGF2 Doege-Potter syndrome
 * CDKN1C Beckwith-Wiedemann syndrome
 * GPC3 Simpson-Golabi-Behmel syndrome

Muscle/Cardiac genes

 * MAPK7?heart?
 * GJA1 oculodentodigital dysplasia and heart malformations
 * Cathepsin_L myonecrosis?
 * LMNA Emery-Dreifuss muscular dystrophy myopathy and cardiomyopathy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease

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

Getting closer to new algorithm
''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. ''

=Developmental Disorders= 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
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
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
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
(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
(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

 * 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
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
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.
 * PAX3 Waardenburg syndrome type I
 * MITF Microphthalmia associated transcription factor Tietz syndrome and Waardenburg syndrome type IIA
 * WS2B Waardenburg syndrome type IIB
 * WS2C Waardenburg syndrome type IIC
 * SNAI2 Waardenburg syndrome type IID
 * PAX3 Waardenburg syndrome type III
 * EDNRB Waardenberg-Hirschsprung, Waardenburg-Shah (Waardenberg syndrome type IV
 * EDN3 "   "   "   "   "   "   "   "   "   "   "   "
 * SOX10 "  "   "   "   "   "   "   "   "   "   "   "
 * TRIM50 William syndrome
 * MYOZ3 Myozenin 3
 * IRF6 Interferon regulatory factor; important in keratinocyte developmentvan der Woude syndrome or popliteal pterygium syndrome
 * EYA1 (Homologous to the eyes absent gene in drosophila) branchiootorenal dysplasia syndrome, branchiootic syndrome, and sporadic cases of congenital cataracts and ocular anterior segment anomalies
 * CHD7 CHARGE syndrome
 * TCOF1 Treacher Collins syndrome
 * OFD1 oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2
 * EXT1, 2, 3
 * LMX1A or B
 * SHOX
 * GNAS1

Cartilage genes
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.
 * GLB1
 * GALN5
 * BGAL
 * GNPT
 * IDUA
 * IDS
 * SGSH
 * NAGLU
 * HGSNAT
 * GNS
 * COL2A1 achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type
 * SOX9 (regulates COL2A) Campomelic dysplasia
 * COL11A1
 * TRPS1
 * ATRX
 * MIDI
 * PHCR7
 * LIMK1
 * ROR2
 * FGD1
 * TRIM(achondroplasia?)

Cranial genes
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

 * CLCN7
 * ATP6
 * POR
 * FGFR1,2,3,4,10
 * TWIST

Secondary Craniosynostosis
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."
 * HSPC2
 * DMI
 * PEX
 * COH1
 * GLI3

Brain genes
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.


 * GLI3
 * LICAM
 * POMTI
 * LISI
 * ATM
 * ATP7A
 * SNRPN
 * UBE3A
 * FBN3 Fibrillin 3

Musculoskeletal genes
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.
 * SALL1
 * FLNA
 * RPS6KA3
 * COMP
 * COL9A1, 2, 3
 * COL2A1
 * SOX9
 * DYM
 * FLNB
 * RMRP
 * PTHRP
 * SBDS
 * EBP
 * ARSE
 * PEX7
 * TNSALP
 * MAPK7
 * GJA1
 * Cathepsin_L
 * RUNX2
 * ANKH

Limb defects

 * GDF5
 * TBX3
 * TBX5
 * NSDHL
 * RPS19

Overgrowth Syndromes

 * FBN1
 * FMR1
 * NSD1
 * IGF2
 * CDKN1C
 * GPC3

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