Assignment/Exam
Description
Written Assignments: These assignments are designed to get you to use original
scientific reports (not review articles) to describe and critique an
unfolding paradigm. Try to draw the “big picture” while
reinforcing your interpretations using specific details from the
readings. In essence, I want you to try and write a comprehensive
encyclopedia entry for the DevoDictionary. You chose a gene to start
with (no more than one person per gene please). The assignment
comprises of three components.
1.
Bibliography
The first part requires that you:
a) choose a gene from the appended list – sign up sheet outside my
office – no more than one student per gene please;
b) submit a preliminary bibliography of 5 related articles to
which you will refer in your DevoDictionary (these must be
original research papers, not reviews - if they lack a Material &
Methods, or Experimental Procedures section, they are a review
article);
c) append a printed copy of the first page of each article (not a
downloaded Medline abstract): .p I want to be sure that you have
actually acquired a copy of a few articles.
2. DevoDictionary Page
The second part requires that you create the text for a single
dictionary entry for the DevoDictionary and then to edit a page by one
of your colleagues. Somebody in turn will be editing yours. For
the Dictionary entry, you will need to “fill in the blanks” for the
template that I provide (go to the "New Dictionary" page, and Login
using your UWin ID and password. Generally you can author text in
MS Word (NO FORMATING - this gets stripped), and then cut and paste into
the template provided, and under the heading provided. Choose a gene not
already covered, and be sure to stake your turf by putting the gene name
on a list outside my office door so that nobody else chooses the same
gene or topic (maximum of one person per gene or topic). If you
see a currently posted gene description that is out of date or poorly
done, you may, with my prior permission, elect to update and edit
one instead. Download or scan images (150 dpi minimum) of knockout
phenotypes or expression patterns for incorporation into your page
with short descriptive legends. USE YOUR OWN WORDS PLEASE AND CITE
YOUR REFERENCES - many of the posted pages do not, and were penalized,
so do not be misled. Do not cut and paste text from the web, and
do not paraphrase. I'd prefer that you do not employ quotes either - I
want to read YOUR summary/synthesis in YOUR own words. Don’t
forget to provide a References Cited section and to annotate the origin
of the images. Include links to other pertinent sites, and make
sure that these sites are specific, not generic. It is helpful to
provide a few words of description for each link Check the list of pages
already present in the dictionary (on the 55-355 website). You can also
peek at an example
(go to the page Arx2 in Xenopus which I have written as an example that
would hit a mid to high B grade) to get an idea for how much/little is
required. Note that at the time of writing this sample page, neither the
genomic structure of the gene, nor the number of mRNA isoforms was
known. This information would normally be a part of mammalian, fly, and
fish gene pages. Submit it
online.
3. Edit a Colleague's Page
The third phase is for you to edit the work of a colleague. The white
bubbles beside paragraphs and images will permit you to add comments
anonymously. Remember to be polite and professional. The
idea is to be helpful, not offensive. Be thorough - your comments
will be graded. Has the author made the description clear and
accurate? Are the images useful, or just eye-candy? Are the
references and web links useful or generic? Were the web links presented
in a descriptive manner or were they just raw links that had been cut
and pasted? Were parts of the description unclear, confusing, or
muddy? Any errors ("the fpx gene is located in the developing
lens" - the gene is actually present in all cells, it might just
be expressed in the lens). I
am looking for editorial suggestions to correct grammar and spelling, to
make suggestions for smooth reading, and to forward queries like “I
think I understand this… is this what you mean? You might want to
clarify”, or “what does this mean?” or “Consider a diagram
to simplify the explanation”
4. Re-Edit your Own Page and Submit for a Grade
When the editing is done, submit your comments, and you will then be
granted permission to re-edit your own submission, taking into account
the comments of your reviewer (or not - the comments might not be
helpful). FIRST print off a copy for me to mark up, and then
submit your final work for my approval/editing. We will post these for
use as a class-accessible “dictionary” for general use.
Academic Integrity:
All work and ideas from your readings which have been incorporated into
the body of the text will be cited in the text and entered into a
References Cited section. Avoid long quotations and do not
paraphrase - I require YOUR synthesis of ideas and information, and I
wish to see that all of the facts have been properly cited.
Assignments may be assessed using Turnitin.com should I elect to check
for originality. Be sure to keep a copy of your work on hand for your
own records and protection. (In 18 years I haven’t had a paper go
missing, but there is always a first time).
Finding References:
All of the starting references that you need can be obtained
electronically from the Leddy
Library. It is usually easiest to use
search engne to look for pdfs using the title of an article.
All of the topics/genes listed have papers available if you are using a
Uwindsor account via Leddy, or if you are searching while on campus.
Alternatively, you can search the Leddy e-journals collection, and use
the year, volume, page number, and author information to track the
article you are interested in. Ultimately, you will end up at a
link that will permit you to download a pdf file to read or to print
using your own computer.
For genes, it is helpful to Google "Genbank" and "OMIM" (Online Mendelian Inheritance in Man) which are
resources that are both kept up to date and can lead to more links to
articles. From Genbank you can
access other links such as Unigene that compare your gene of interest
across species. Another useful site is E!Ensembl at http://www.ensembl.org
. This site lets you looks at intron/exon structure, mRNA isoforms, and
chromosomal location. For categorizing Homeobox genes check out: http://homeodb.zoo.ox.ac.uk
EXAMS
Mid-Term Exam: The exam
will be run during class time. In past years, the format of the
exam was a combination of short answer, labeled diagram, and short essay type questions.
This may change given the growth in class size.
Final Exam: The
final exam will be similar in format to that of the
mid-term exam. Here is an example
of the midterm, and here is an example of a final
exam.
Most people finish the exams early - I am interested to see
what you know, not how quickly you can write.
GRADING
Grading
scale as set by University of Windsor Senate follows:
A+
90-100%
A
85-89.9%
A- 80-84.9%
B+ 77-79.9%
B
73-76.9%
B- 70-72.9%
C+ 67-69.9%
C
63-66.9%
C- 60-62.9%
D+ 57-59.9%
D
53-56.9%
D- 50-52.9%
Fail Below 50%
1. miR-675
Keniry, A., D. Oxley, P. Monnier, M. Kyba, L. Dandolo, G. Smits, and W.
Reik. 2012. "The H19 lincRNA is a developmental reservoir of miR-675
that suppresses growth and Igf1r." Nat Cell Biol 14 (7):659-65.
doi: 10.1038/ncb2521.
2. Hox C13 Human
Lin Z., Chen Q., Shi L., Lee M., Giehl
K.A., Tang Z., Wang H., Zhang J., Yin J.,
Wu L., Xiao R., Liu X., Dai L., Zhu X., Li
R., Betz R.C., Zhang X., and Yang Y. 2012. Loss-of-function
mutations in HOXC13 cause pure hair and nail ectodermal dysplasia. Am J
Hum Genet 91: 906-911.
3. Huntingtin
Godin J.D., Colombo K., Molina-Calavita M., Keryer
G., Zala D., Charrin B.C., Dietrich P., Volvert
M.L., Guillemot F., Dragatsis I., Bellaiche Y.,
Saudou F., Nguyen L., and Humbert S. 2010. Huntingtin is required
for mitotic spindle orientation and mammalian neurogenesis. Neuron 67:
392-406.
4. LEFTY2 (Human)
Kosaki K., Bassi M.T., Kosaki R., Lewin M.,
Belmont J., Schauer G., and Casey B. 1999. Characterization and
mutation analysis of human LEFTY A and LEFTY B, homologues of murine
genes implicated in left-right axis development. Am J Hum Genet 64:
712-721.
5. lncRNA RNCR2
Rapicavoli N.A., Poth E.M., and Blackshaw S. 2010. The long
noncoding RNA RNCR2 directs mouse retinal cell specification. BMC Dev
Biol 10: 49.
6. HoxB1 (mouse)
Studer M., Lumsden A., Ariza-McNaughton L., Bradley
A., and Krumlauf R. 1996. Altered segmental identity and abnormal
migration of motor neurons in mice lacking Hoxb-1. Nature 384: 630-634.
7. HoxA2 (mouse)
Gavalas A., Davenne M., Lumsden A., Chambon P., and
Rijli F.M. 1997. Role of Hoxa-2 in axon pathfinding and rostral
hindbrain patterning. Development 124: 3693-3702.
8. HoxA10 (Mice)
Satokata I., Benson G., and Maas R. 1995. Sexually dimorphic
sterility phenotypes in Hoxa10-deficient mice. Nature 374: 460-463.
9. Even-skipped (fruitfly)
McDonald J.A., Fujioka M., Odden J.P., Jaynes J.B.,
and Doe C.Q. 2003. Specification of motoneuron fate in Drosophila:
integration of positive and negative transcription factor inputs by a
minimal eve enhancer. J Neurobiol 57: 193-203.
10. Evx1 Mouse only
Thaeron C., Avaron F., Casane D., Borday V.,
Thisse B., Thisse C., Boulekbache H., and Laurenti P. 2000.
Zebrafish evx1 is dynamically expressed during embryogenesis in subsets
of interneurones, posterior gut and urogenital system. Mech Dev 99:
167-172.
11. Hoxb8 (mouse only))
Greer J.M., and Capecchi M.R. 2002. Hoxb8 is required for normal
grooming behavior in mice. Neuron 33: 23-34.
12. Meis1 (mouse only)
Mercader N., Selleri L., Criado L.M., Pallares
P., Parras C., Cleary M.L., and Torres M. 2009. Ectopic
Meis1 expression in the mouse limb bud alters P-D patterning in a
Pbx1-independent manner. Int J Dev Biol 53: 1483-1494.
13. POU1F1 (Pit1)
Nica G., Herzog W., Sonntag C., and Hammerschmidt M. 2004.
Zebrafish pit1 mutants lack three pituitary cell types and develop
severe dwarfism. Mol Endocrinol 18: 1196-1209.
14. Pit1 human
Fofanova, O. V., N. Takamura, E. Kinoshita, M. Yoshimoto, Y. Tsuji, V.
A. Peterkova, O. V. Evgrafov, Dedov, II, N. P. Goncharov, and S.
Yamashita. 1998. "Rarity of PIT1 involvement in children from Russia
with combined pituitary hormone deficiency." Am J Med Genet 77
(5):360-5.
15. Gbx1 (mouse)
Buckley D.M., Burroughs-Garcia J., Lewandoski M., and Waters
S.T. 2013. Characterization of the Gbx1-/- mouse mutant: a requirement
for Gbx1 in normal locomotion and sensorimotor circuit development. PLoS
One 8: e56214.
16. lncRNA Evf-2
Feng J., Bi C., Clark B.S., Mady R., Shah P.,
and Kohtz J.D. 2006. The Evf-2 noncoding RNA is transcribed from the
Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional
coactivator. Genes Dev 20: 1470-1484.
17. ncRNA Fendrr
Grote P., Wittler L., Hendrix D., Koch F.,
Wahrisch S., Beisaw A., Macura K., Blass G.,
Kellis M., Werber M., and Herrmann B.G. 2013. The tissue-specific
lncRNA Fendrr is an essential regulator of heart and body wall
development in the mouse. Dev Cell 24: 206-214.
18. miR-126
Fish J.E., Santoro M.M., Morton S.U., Yu S., Yeh
R.F., Wythe J.D., Ivey K.N., Bruneau B.G.,
Stainier D.Y., and Srivastava D. 2008. miR-126 regulates angiogenic
signaling and vascular integrity. Dev Cell 15: 272-284.
19. lncRNA Kcnq1ot1
Redrup L., Branco M.R., Perdeaux E.R., Krueger
C., Lewis A., Santos F., Nagano T., Cobb
B.S., Fraser P., and Reik W. 2009. The long noncoding RNA Kcnq1ot1
organises a lineage-specific nuclear domain for epigenetic gene
silencing. Development 136: 525-530.
20. ACE - angiotensin-converting enzyme and muscle performance
Scott R.A., Irving R., Irwin L., Morrison E.,
Charlton V., Austin K., Tladi D., Deason M.,
Headley S.A., Kolkhorst F.W., Yang N., North K., and
Pitsiladis Y.P. 2010. ACTN3 and ACE genotypes in elite Jamaican and US
sprinters. Med Sci Sports Exerc 42: 107-112.
21. Brinp
Kawano H., Nakatani T., Mori T., Ueno S., Fukaya
M., Abe A., Kobayashi M., Toda F., Watanabe M.,
and Matsuoka I. 2004. Identification and characterization of novel
developmentally regulated neural-specific proteins, BRINP family. Brain
Res Mol Brain Res 125: 60-75.
22. DYNAMIN 2; DNM2 (human only )
Bitoun, M., Maugenre, S., Jeannet, P.-Y., Lacene, E., Ferrer, X.,
Laforet, P., Martin, J.-J., Laporte, J., Lochmuller, H., Beggs, A. H.,
Fardeau, M., Eymard, B., Romero, N. B., Guicheney, P. Mutations in
dynamin 2 cause dominant centronuclear myopathy. Nature Genet. 37:
1207-1209, 2005.
23. DYNAMIN 2; DNM2 (human) (mouse only)
Durieux, A.-C., Vignaud, A., Prudhon, B., Viou, M. T., Beuvin, M.,
Vassilopoulos, S., Fraysse, B., Ferry, A., Laine, J., Romero, N. B.,
Guicheney, P., Bitoun, M. A centronuclear myopathy-dynamin 2 mutation
impairs skeletal muscle structure and function in mice. Hum. Molec.
Genet. 19: 4820-4836, 2010.
24. IDURONIDASE, ALPHA-L (human)
Aronovich, E. L., Pan, D., Whitley, C. B. Molecular genetic defect
underlying alpha-L-iduronidase pseudodeficiency. Am. J. Hum. Genet. 58:
75-85, 1996.
25. HYPOCRETIN; HCRT (mouse only)
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K.,
Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y.,
Kisanuki, Y., Fitch, T. E., Nakazato, M., Hammer, R. E., Saper, C. B.,
Yanagisawa, M. Narcolepsy in orexin knockout mice: molecular genetics of
sleep regulation. Cell 98: 437-451, 1999.
26. HYPOCRETIN; HCRT (human only)
Thannickal, T. C., Moore, R. Y., Nienhuis, R., Ramanathan, L., Gulyani,
S., Aldrich, M., Cornford, M., Siegel, J. M. Reduced number of
hypocretin neurons in human narcolepsy. Neuron 27: 469-474, 2000.
27. BETA-GLUCURONIDASE; GUSB (human only)
Vervoort, R., Gitzelmann, R., Lissens, W., Liebaers, I. A mutation
(IVS8+0.6kbdelTC) creating a new donor splice site activates a cryptic
exon in an Alu-element in intron 8 of the human beta-glucuronidase gene.
Hum. Genet. 103: 686-693, 1998.
27.B BETA-GLUCURONIDASE; GUSB (mouse only)
Tomatsu, S., Orii, K. O., Vogler, C., Grubb, J. H., Snella, E. M.,
Gutierrez, M. A., Dieter, T., Sukegawa, K., Orii, T., Kondo, N., Sly, W.
S. Missense models [Gus(tm(E536A)Sly), Gus(tm(E536Q)Sly), and
Gus(tm(L175F)Sly)] of murine mucopolysaccharidosis type VII produced by
targeted mutagenesis. Proc. Nat. Acad. Sci. 99: 14982-14987, 2002.
28. Alx4 (human only)
Wuyts, W., Cleiren, E., Homfray, T., Rasore-Quartino, A., Vanhoenacker,
F., Van Hul, W. The ALX4 homeobox gene is mutated in patients with
ossification defects of the skull (foramina parietalia permagna, OMIM
168500). J. Med. Genet. 37: 916-920, 2000.
29. Alx4 (mouse only)
Qu, S., Tucker, S. C., Ehrlich, J. S., Levorse, J. M., Flaherty, L. A.,
Wisdom, R., Vogt, T. F. Mutations in mouse Aristaless-like4 cause
Strong's luxoid polydactyly. Development 125: 2711-2721, 1998.
30. ACTIVIN A RECEPTOR, TYPE I; ACVR1 (human only)
Shore, E. M., Xu, M., Feldman, G. J., Fenstermacher, D. A., Cho, T.-J.,
Choi, I. H., Connor, J. M., Delai, P., Glaser, D. L., LeMerrer, M.,
Morhart, R., Rogers, J. G., Smith, R., Triffitt, J. T., Urtizberea, J.
A., Zasloff, M., Brown, M. A., Kaplan, F. S. A recurrent mutation in the
BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia
ossificans progressiva. Nature Genet. 38: 525-527, 2006.
31. ACTIVIN A RECEPTOR, TYPE I; ACVR1 (mouse only)
Yu, P. B., Deng, D. Y., Lai, C. S., Hong, C. C., Cuny, G. D., Bouxsein,
M. L., Hong, D. W., McManus, P. M., Katagiri, T., Sachidanandan, C.,
Kamiya, N., Fukuda, T., Mishina, Y., Peterson, R. T., Bloch, K. D. BMP
type I receptor inhibition reduces heterotopic ossification. Nature Med.
14: 1363-1369, 2008.
32. HOLOCYTOCHROME C SYNTHASE; HCCS (human only) Wimplinger, I., Morleo,
M., Rosenberger, G., Iaconis, D., Orth, U., Meinecke, P., Lerer, I.,
Ballabio, A., Gal, A., Franco, B., Kutsche, K. Mutations of the
mitochondrial holocytochrome c-type synthase in X-linked dominant
microphthalmia with linear skin defects syndrome. Am. J. Hum. Genet. 79:
878-889, 2006.
33. HOLOCYTOCHROME C SYNTHASE; HCCS (mouse only)
Prakash, S. K., Cormier, T. A., McCall, A. E., Garcia, J. J., Sierra,
R., Haupt, B., Zoghbi, H. Y., Van den Veyver, I. B. Loss of
holocytochrome c-type synthetase causes the male lethality of X-linked
dominant microphthalmia with linear skin defects (MLS) syndrome. Hum.
Molec. Genet. 11: 3237-3248, 2002.
34. ANOCTAMIN 5; ANO5 (human only)
Tsutsumi, S., Kamata, N., Vokes, T. J., Maruoka, Y., Nakakuki, K.,
Enomoto, S., Omura, K., Amagasa, T., Nagayama, M., Saito-Ohara, F.,
Inazawa, J., Moritani, M., Yamaoka, T., Inoue, H., Itakura, M. The novel
gene encoding a putative transmembrane protein is mutated in
gnathodiaphyseal dysplasia (GDD). Am. J. Hum. Genet. 74: 1255-1261,
2004.
35. NEUROFIBROMIN 1; NF1 (human only)
Gervasini, C., Bentivegna, A., Venturin, M., Corrado, L., Larizza, L.,
Riva, P. Tandem duplication of the NF1 gene detected by high-resolution
FISH in the 17q11.2 region. Hum. Genet. 110: 314-321, 2002.
36. NEUROFIBROMIN 1; NF1 (mouse only)
Kolanczyk, M., Kossler, N., Kuhnisch, J., Lavitas, L., Stricker, S.,
Wilkening, U., Manjubala, I., Fratzl, P., Sporle, R., Herrmann, B. G.,
Parada, L. F., Kornak, U., Mundlos, S. Multiple roles for neurofibromin
in skeletal development and growth. Hum. Molec. Genet. 16: 874-886,
2007.
37. CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 7; CHD7 (human only)
Jongmans, M. C. J., Admiraal, R. J., van der Donk, K. P., Vissers, L. E.
L. M., Baas, B. F., Kapusta, L., van Hagen, J. M., Donnai, D., de Ravel,
T. J., Veltman, J. A., Geurts van Kessel, A., De Vries, B. B. A.,
Brunner, H. G., Hoefsloot, L. H., van Ravenswaaij, C. M. A. CHARGE
syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J. Med.
Genet. 43: 306-314, 2006.
38. CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 7; CHD7 (mouse only)
Bosman, E. A., Penn, A. C., Ambrose, J. C., Kettleborough, R., Stemple,
D. L., Steel, K. P. Multiple mutations in mouse Chd7 provide models for
CHARGE syndrome. Hum. Molec. Genet. 14: 3463-3476, 2005.
39. HEART- AND NEURAL CREST DERIVATIVES-EXPRESSED 1; HAND1 (mouse only)
Firulli, A. B., McFadden, D. G., Lin, Q., Srivastava, D., Olson, E. N.
Heart and extra-embryonic mesodermal defects in mouse embryos lacking
the bHLH transcription factor Hand1. Nature Genet. 18: 266-270, 1998.
40. T-BOX 2; TBX2 (mouse only)
Harrelson, Z., Kelly, R. G., Goldin, S. N., Gibson-Brown, J. J., Bollag,
R. J., Silver, L. M., Papaioannou, V. E. Tbx2 is essential for
patterning the atrioventricular canal and for morphogenesis of the
outflow tract during heart development. Development 131: 5041-5052,
2004.
41. POLYCYSTIN 1; PKD1 (human only)
European Polycystic Kidney Disease Consortium. The polycystic kidney
disease 1 gene encodes a 14 kb transcript and lies within a duplicated
region on chromosome 16. Cell 77: 881-894, 1994.
42. POLYCYSTIN 1; PKD1 (mouse only)
Lu, W., Peissel, B., Babakhanlou, H., Pavlova, A., Geng, L., Fan, X.,
Larson, C., Brent, G., Zhou, J. Perinatal lethality with kidney and
pancreas defects in mice with a targeted Pkd1 mutation. Nature Genet.
17: 179-181, 1997.
43. POLYCYSTIN 2; PKD2 (human only)
Mochizuki, T., Wu, G., Hayashi, T., Xenophontos, S. L., Veldhuisen, B.,
Saris, J. J., Reynolds, D. M., Cai, Y., Gabow, P. A., Pierides, A.,
Kimberling, W. J., Breuning, M. H., Constantinou Deltas, C., Peters, D.
J. M., Somlo, S. PKD2, a gene for polycystic kidney disease that encodes
an integral membrane protein. Science 272: 1339-1342, 1996.
44. POLYCYSTIN 2; PKD2 (mouse only)
Wu, G., Markowitz, G. S., Li, L., D'Agati, V. D., Factor, S. M., Geng,
L., Tibara, S., Tuchman, J., Cai, Y., Park, J. H., van Adelsberg, J.,
Hou, H., Jr., Kucherlapati, R., Edelmann, W., Somlo, S. Cardiac defects
and renal failure in mice with targeted mutations in Pkd2. Nature Genet.
24: 75-78, 2000.
45. Sall1 (human only)
Kohlhase, J., Wischermann, A., Reichenbach, H., Froster, U., Engel, W.
Mutations in the SALL1 putative transcription factor gene cause
Townes-Brocks syndrome. Nature Genet. 18: 81-83, 1998.
46. Sall1 (fly only)
Si Dong, P. D., Todi, S. V., Eberl, D. F., Boekhoff-Falk, G. Drosophila
spalt/spalt-related mutants exhibit Townes-Brocks' syndrome phenotypes.
Proc. Nat. Acad. Sci. 100: 10293-10298, 2003.
47. Endothelin 1 EDN1 (human only)
Wiltshire, S., Powell, B. L., Jennens, M., McCaskie, P. A., Carter, K.
W., Palmer, L. J., Thompson, P. L., McQuillan, B. M., Hung, J., Beilby,
J. P. Investigating the association between K198N coding polymorphism in
EDN1 and hypertension, lipoprotein levels, the metabolic syndrome and
cardiovascular disease. Hum. Genet. 123: 307-313, 2008.
48. KCNH1 (mouse only)
Ufartes, R., Schneider, T., Motensen, L. S., de Juan Romero, C.,
Hentrich, K., Knoetgen, H., Beilinson, V., Moebius, W., Tarabykin, V.,
Alves, F., Pardo, L. A., Rawlins, J. N. P., Stuehmer, W. Behavioural and
functional characterization of K(v)10.1 (Eag1) knockout mice. Hum.
Molec. Genet. 22: 2247-2262, 2013.
49. KCNH1 (human only)
Simons, C., Rash, L. D., Crawford, J., Ma, L., Cristofori-Armstrong, B.,
Miller, D., Ru, K., Baillie, G. J., Alanay, Y., Jacquinet, A., Debray,
F.-G., Verloes, A., and 10 others. Mutations in the voltage-gated
potassium channel gene KCNH1 cause Temple-Baraitser syndrome and
epilepsy. Nature Genet. 47: 73-77, 2015.
50. ORC1 (Human only)
Bicknell, L. S., Walker, S., Klingseisen, A., Stiff, T., Leitch, A.,
Kerzendorfer, C., Martin, C.-A., Yeyati, P., Al Sanna, N., Bober, M.,
Johnson, D., Wise, C., Jackson, A. P., O'Driscoll, M., Jeggo, P. A.
Mutations in ORC1, encoding the largest subunit of the origin
recognition complex, cause microcephalic primordial dwarfism resembling
Meier-Gorlin syndrome. Nature Genet. 43: 350-355, 2011.
51 Geminin (human only)
Burrage, L. C., Charng, W.-L., Eldomery, M. K., Willer, J. R., Davis, E.
E., Lugtenberg, D., Zhu, W., Leduc, M. S., Akdemir, Z. C., Azamian, M.,
Zapata, G., Hernandez, P. P., and 18 others. De novo GMNN mutations
cause autosomal-dominant primordial dwarfism associated with
Meier-Gorlin syndrome. Am. J. Hum. Genet. 97: 904-913, 2015.
52. Geminin (mouse only)
Gonzalez, M. A., Tachibana, K. K., Adams, D. J., van der Weyden, L.,
Hemberger, M., Coleman, N., Bradley, A., Laskey, R. A. Geminin is
essential to prevent endoreduplication and to form pluripotent cells
during mammalian development. Genes Dev. 20: 1880-1884, 2006.
53. Frem1 (mouse only)
Smyth, I., Du, X., Taylor, M. S., Justice, M. J., Beutler, B., Jackson,
I. J. The extracellular matrix gene Frem1 is essential for the normal
adhesion of the embryonic epidermis. Proc. Nat. Acad. Sci. 101:
13560-13565, 2004.
54. FREM1 (human only)
Vissers, L. E. L. M., Cox, T. C., Maga, A. M., Short, K. M., Wiradjaja,
F., Janssen, I. M., Jehee, F., Bertola, D., Liu, J., Yagnik, G.,
Sekiguchi, K., Kiyozumi, D., and 10 others. Heterozygous mutations of
FREM1 are associated with an increased risk of isolated metopic
craniosynostosis in humans and mice. PLoS Genet. 7: e1002278, 2011.
55. HSPA9 (human)
Schmitz-Abe, K., Ciesielski, S. J., Schmidt, P. J., Campagna, D. R.,
Rahimov, F., Schilke, B. A., Cuijpers, M., Rieneck, K., Lausen, B.,
Linenberger, M. L., Sendamarai, A. K., Guo, C., and 16 others.
Congenital sideroblastic anemia due to mutations in the mitochondrial
HSP70 homologue HSPA9. Blood 126: 2734-2738, 2015.
56. NOG (human only))
Gong, Y., Krakow, D., Marcelino, J., Wilkin, D., Chitayat, D.,
Babul-Hirji, R., Hudgins, L., Cremers, C. W., Cremers, F. P. M.,
Brunner, H. G., Reinker, K., Rimoin, D. L., Cohn, D. H., Goodman, F. R.,
Reardon, W., Patton, M., Francomano, C. A., Warman, M. L. Heterozygous
mutations in the gene encoding noggin affect human joint morphogenesis.
Nature Genet. 21: 302-304, 1999.
57. FAMILY WITH SEQUENCE SIMILARITY 58, MEMBER A; FAM58A
Unger, S., Bohm, D., Kaiser, F. J., Kaulfuss, S., Borozdin, W., Buiting,
K., Burfeind, P., Bohm, J., Barrionuevo, F., Craig, A., Borowski, K.,
Keppler-Noreuil, K., and 9 others. Mutations in the cyclin family member
FAM58A cause an X-linked dominant disorder characterized by syndactyly,
telecanthus and anogenital and renal malformations. Nature Genet. 40:
287-289, 2008.
58. COLLAGEN, TYPE II, ALPHA-1; COL2A1 (human only)
Godfrey, M., Hollister, D. W. Type II
achondrogenesis-hypochondrogenesis: identification of abnormal type II
collagen. Am. J. Hum. Genet. 43: 904-913, 1988.
59. COLLAGEN, TYPE II, ALPHA-1; COL2A1 (mouse only)
Vandenberg, P., Khillan, J. S., Prockop, D. J., Helminen, H.,
Kontusaari, S., Ala-Kokko, L. Expression of a partially deleted gene of
a human type II procollagen (COL2A1) in transgenic mice produces a
chondrodysplasia. Proc. Nat. Acad. Sci. 88: 7640-7644, 1991.
60. CBP (mouse only)
Tanaka, Y., Naruse, I., Maekawa, T., Masuya, H., Shiroishi, T., Ishii,
S. Abnormal skeletal patterning in embryos lacking a single Cbp allele:
a partial similarity with Rubinstein-Taybi syndrome. Proc. Nat. Acad.
Sci. 94: 10215-10220, 1997.
61. DISCOIDIN DOMAIN RECEPTOR FAMILY, MEMBER 2; DDR2 (mouse only)
Labrador, J. P., Azcoitia, V., Tuckermann, J., Lin, C., Olaso, E.,
Manes, S., Bruckner, K., Goergen, J.-L., Lemke, G., Yancopoulos, G.,
Angel, P., Martinez-A, C., Klein, R. The collagen receptor DDR2
regulates proliferation and its elimination leads to dwarfism. EMBO J.
2: 446-452, 2001.
62. DISCOIDIN DOMAIN RECEPTOR FAMILY, MEMBER 2; DDR2 (human only)
Bargal, R., Cormier-Daire, V., Ben-Neriah, Z., Le Merrer, M., Sosna, J.,
Melki, J., Zangen, D. H., Smithson, S. F., Borochowitz, Z., Belostotsky,
R., Raas-Rothschild, A. Mutations in DDR2 gene cause SMED with short
limbs and abnormal calcifications. Am. J. Hum. Genet. 84: 80-84, 2009.
63. CRYSTALLIN, GAMMA-D; CRYGD (human only)
Santhiya, S. T., Manohar, M. S., Rawlley, D., Vijayalakshmi, P.,
Namperumalsamy, P., Gopinath, P. M., Loster, J., Graw, J. Novel
mutations in the gamma-crystallin genes cause autosomal dominant
congenital cataracts. J. Med. Genet. 39: 352-358, 2002.
64. CRYSTALLIN, GAMMA-D; CRYGD (mouse only)
Smith, R. S., Hawes, N. L., Chang, B., Roderick, T. H., Akeson, E. C.,
Heckenlively, J. R., Gong, X., Wang, X., Davisson, M. T. Lop12, a
mutation in mouse Crygd causing lens opacity similar to human Coppock
cataract. Genomics 63: 314-320, 2000.
65. GAP JUNCTION PROTEIN, ALPHA-8; GJA8
Berry, V., Mackay, D., Khaliq, S., Francis, P. J., Hameed, A., Anwar,
K., Mehdi, S. Q., Newbold, R. J., Ionides, A., Shiels, A., Moore, T.,
Bhattacharya, S. S. Connexin 50 mutation in a family with congenital
'zonular nuclear' pulverulent cataract of Pakistani origin. Hum. Genet.
105: 168-170, 1999.
66. Talpid3 (zebrafish)
Ben, J., S. Elworthy, A. S. Ng, F. van Eeden, and P. W. Ingham. 2011.
"Targeted mutation of the talpid3 gene in zebrafish reveals its
conserved requirement for ciliogenesis and Hedgehog signalling across
the vertebrates." Development 138 (22):4969-78. doi:
10.1242/dev.070862.
67. DNA Primase
Yamaguchi, M., N. Fujimori-Tonou, Y. Yoshimura, T. Kishi, H. Okamoto,
and I. Masai. 2008. "Mutation of DNA primase causes extensive apoptosis
of retinal neurons through the activation of DNA damage checkpoint and
tumor suppressor p53." Development 135 (7):1247-57.
68. alpha tubulin (mouse)
Gartz Hanson M., Aiken J., Sietsema D.V., Sept
D., Bates E.A., Niswander L., and Moore J.K. 2016. Novel
alpha-tubulin mutation disrupts neural development and tubulin
proteostasis. Dev Biol 409: 406-419.
69. Smc5
Pryzhkova, M. V., and P. W. Jordan. 2016. "Conditional mutation of Smc5
in mouse embryonic stem cells perturbs condensin localization and
mitotic progression." Development 143 (9):e1 2. doi:
10.1242/dev.138776.
70. Cloche (Zebrafish)
Dhakal, S., C. B. Stevens, M. Sebbagh, O. Weiss, R. A. Frey, S. Adamson,
E. A. Shelden, A. Inbal, and D. L. Stenkamp. 2015. "Abnormal retinal
development in Cloche mutant zebrafish." Dev Dyn 244 (11):1439-55.
doi: 10.1002/dvdy.24322.
71. twsg1
Billington, C. J., Jr., B. Schmidt, R. S. Marcucio, B. Hallgrimsson, R.
Gopalakrishnan, and A. Petryk. 2015. "Impact of retinoic acid exposure
on midfacial shape variation and manifestation of holoprosencephaly in
Twsg1 mutant mice." Dis Model Mech 8 (2):139-46. doi:
10.1242/dmm.018275.
72. Gli2 (mouse only)
Grachtchouk, M., Mo, R., Yu, S., Zhang, X., Sasaki, H., Hui, C.,
Dlugosz, A. A. Basal cell carcinomas in mice overexpressing Gli2 in
skin. (Letter) Nature Genet. 24: 216-217, 2000.
73. Gli2 (human only)
Roessler, E., Du, Y.-Z., Mullor, J. L., Casas, E., Allen, W. P.,
Gillessen-Kaesbach, G., Roeder, E. R., Ming, J. E., Ruiz i Altaba, A.,
Muenke, M. Loss-of-function mutations in the human GLI2 gene are
associated with pituitary anomalies and holoprosencephaly-like features.
Proc. Nat. Acad. Sci. 100: 13424-13429, 2003.
74. PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE, PAFAH1B1
Uyanik, G., Morris-Rosendahl, D. J., Stiegler, J., Klapecki, J., Gross,
C., Berman, Y., Martin, P., Dey, L., Spranger, S., Korenke, G. C.,
Schreyer, I., Hertzberg, C., and 25 others. Location and type of
mutation in the LIS1 gene do not predict phenotypic severity. Neurology
69: 442-447
75. LIMB REGION 1, MOUSE, HOMOLOG OF; LMBR1 (human only – not sonic
hedgehog)
Ianakiev, P., van Baren, M. J., Daly, M. J., Toledo, S. P. A.,
Cavalcanti, M. G., Neto, J. C., Silveira, E. L., Freire-Maia, A.,
Heutink, P., Kilpatrick, M. W., Tsipouras, P. Acheiropodia is caused by
a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene.
Am. J. Hum. Genet. 68: 38-45, 2001.
76. LIMB REGION 1, MOUSE, HOMOLOG OF; LMBR1 (mouse only – not sonic
hedgehog)
Lettice, L. A., Hill, A. E., Devenney, P. S., Hill, R. E. Point
mutations in a distant sonic hedgehog cis-regulator generate a variable
regulatory output responsible for preaxial polydactyly. Hum. Molec.
Genet. 17: 978-985, 2008
77. BBS4 GENE; BBS4 (mouse only)
Kulaga, H. M., Leitch, C. C., Eichers, E. R., Badano, J. L., Lesemann,
A., Hoskins, B. E., Lupski, J. R., Beales, P. L., Reed, R. R., Katsanis,
N. Loss of BBS proteins causes anosmia in humans and defects in
olfactory cilia structure and function in the mouse. Nature Genet. 36:
994-998, 2004.
78. BBS4 GENE; BBS4 (human only)
Mykytyn, K., Braun, T., Carmi, R., Haider, N. B., Searsby, C. C.,
Shastri, M., Beck, G., Wright, A. F., Iannaccone, A., Elbedour, K.,
Riise, R., Baldi, A., Raas-Rothschild, A., Gorman, S. W., Duhl, D. M.,
Jacobson, S. G., Casavant, T., Stone, E. M., Sheffield, V. C.
Identification of the gene that, when mutated, causes the human obesity
syndrome BBS4. Nature Genet. 28: 188-191, 2001.
79. FIBROBLAST GROWTH FACTOR RECEPTOR 1; FGFR1 (human only)
Muenke, M., Schell, U., Hehr, A., Robin, N. H., Losken, H. W., Schinzel,
A., Pulleyn, L. J., Rutland, P., Reardon, W., Malcolm, S., Winter, R. M.
A common mutation in the fibroblast growth factor receptor 1 gene in
Pfeiffer syndrome. Nature Genet. 8: 269-274, 1994.
80. ELONGATOR ACETYLTRANSFERASE COMPLEX, SUBUNIT 4; ELP4 (human only)
Bhatia, S., Bengani, H., Fish, M., Brown, A., Divizia, M. T., de Marco,
R., Damante, G., Grainger, R., van Heyningen, V., Kleinjan, D. A.
Disruption of autoregulatory feedback by a mutation in a remote,
ultraconserved PAX6 enhancer causes aniridia. Am. J. Hum. Genet. 93:
1126-1134, 2013.
81. PROMININ 1; PROM1 (Human only)
Zhang, Q., Zulfiqar, F., Xiao, X., Riazuddin, S. A., Ahmad, Z., Caruso,
R., MacDonald, I., Sieving, P., Riazuddin, S., Hejtmancik, J. F. Severe
retinitis pigmentosa mapped to 4p15 and associated with a novel mutation
in the PROM1 gene. Hum. Genet. 122: 293-299, 2007.
82. Prominin 1 ; Prom1 (Mouse only)
Zhu, L., Gibson, P., Currle, D. S., Tong, Y., Richardson, R. J.,
Bayazitov, I. T., Poppleton, H., Zakharenko, S., Ellison, D. W.,
Gilbertson, R. J. Prominin 1 marks intestinal stem cells that are
susceptible to neoplastic transformation. Nature 457: 603-607, 2009.
83. HNF1 HOMEOBOX B; HNF1B (mouse only)
Maestro, M. A., Boj, S. F., Luco, R. F., Pierreux, C. E., Cabedo, J.,
Servitja, J. M., German, M. S., Rousseau, G. G., Lemaigre, F. P.,
Ferrer, J. Hnf6 and Tcf2 (MODY5) are linked in a gene network operating
in a precursor cell domain of the embryonic pancreas. Hum. Molec. Genet.
12: 3307-3314, 2003.
84. HNF1 HOMEOBOX B; HNF1B (Xenopus only)
Wild, W., Pogge von Strandmann, E., Nastos, A., Senkel, S.,
Lingott-Frieg, A., Bulman, M., Bingham, C., Ellard, S., Hattersley, A.
T., Ryffel, G. U. The mutated human gene encoding hepatocyte nuclear
factor 1-beta inhibits kidney formation in developing Xenopus embryos.
Proc. Nat. Acad. Sci. 97: 4695-4700, 2000.
85. HNF1 HOMEOBOX B; HNF1B (Human only)
Lindner, T. H., Njolstad, P. R., Horikawa, Y., Bostad, L., Bell, G. I.,
Sovik, O. A novel syndrome of diabetes mellitus, renal dysfunction and
genital malformation associated with a partial deletion of the
pseudo-POU domain of hepatocyte nuclear factor-1-beta. Hum. Molec.
Genet. 8: 2001-2008, 1999.
86. CHOLINERGIC RECEPTOR, MUSCARINIC, 3; CHRM3 (mouse only)
Matsui, M., Motomura, D., Karasawa, H., Fujikawa, T., Jiang, J., Komiya,
Y., Takahashi, S., Taketo, M. M. Multiple functional defects in
peripheral autonomic organs in mice lacking muscarinic acetylcholine
receptor gene for the M3 subtype. Proc. Nat. Acad. Sci. 97: 9579-9584,
2000.
87. CHOLINERGIC RECEPTOR, MUSCARINIC, 3; CHRM3 (human only)
Weber, S., Thiele, H., Mir, S., Toliat, M. R., Sozeri, B., Reutter, H.,
Draaken, M., Ludwig, M., Altmuller, J., Frommolt, P., Stuart, H. M.,
Ranjzad, P., and 12 others. Muscarinic acetylcholine receptor M3
mutation causes urinary bladder disease and a prune-belly-like syndrome.
Am. J. Hum. Genet. 89: 668-674, 2011.
88. SBDS GENE; SBDS (Human only)
Boocock, G. R. B., Morrison, J. A., Popovic, M., Richards, N., Ellis,
L., Durie, P. R., Rommens, J. M. Mutations in SBDS are associated with
Shwachman-Diamond syndrome. Nature Genet. 33: 97-101, 2003.
89. SBDS GENE; SBDS (mouse only)
Zhang, S., Shi, M., Hui, C., Rommens, J. M. Loss of the mouse ortholog
of the Shwachman-Diamond syndrome gene (Sbds) results in early embryonic
lethality. Molec. Cell Biol. 26: 6656-6663, 2006.
90. PANCREAS/DUODENUM HOMEOBOX PROTEIN 1; PDX1 (mouse only)
Jonnson, J., Carlsson, L., Edlund, T., Edlund, H.
Insulin-promoter-factor 1 is required for pancreas development in mice.
Nature 371: 606-609, 1994.
91. PANCREAS/DUODENUM HOMEOBOX PROTEIN 1; PDX1 (human only)
Stoffers, D. A., Zinkin, N. T., Stanojevic, V., Clarke, W. L., Habener,
J. F. Pancreatic agenesis attributable to a single nucleotide deletion
in the human IPF1 gene coding sequence. Nature Genet. 15: 106-110, 1997
92. REGULATORY FACTOR X, 6; RFX6 (human only)
Sansbury, F. H., Kirel, B., Caswell, R., Allen, H. L., Flanagan, S. E.,
Hattersley, A. T., Ellard, S., Shaw-Smith, C. J. Biallelic RFX6
mutations can cause childhood as well as neonatal onset diabetes
mellitus. Europ. J. Hum. Genet. 23: 1744-1748, 2015.
93. REGULATORY FACTOR X, 6; RFX6 (mouse only)
Smith, S. B., Qu, H.-Q., Taleb, N. Kishimoto, N. Y., Scheel, D. W., Lu,
Y., Patch, A.-M., Grabs, R., Wang, J., Lynn, F. C., Miyatsuka, T.,
Mitchell, J., and 16 others. Rfx6 directs islet formation and insulin
production in mice and humans. Nature 463: 775-780, 2010.
94. FORKHEAD BOX F1; FOXF1 (human only)
Stankiewicz, P., Sen, P., Bhatt, S. S., Storer, M., Xia, Z., Bejjani, B.
A., Ou, Z., Wiszniewska, J., Driscoll, D. J., Maisenbacher, M. K.,
Bolivar, J., Bauer, M., and 32 others. Genomic and genic deletions of
the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1
cause alveolar capillary dysplasia and other malformations. Am. J. Hum.
Genet. 84: 780-791, 2009.
95. FORKHEAD BOX F1; FOXF1 (mouse only)
Kalinichenko, V. V., Zhou, Y., Bhattacharyya, D., Kim, W., Shin, B.,
Bambal, K., Costa, R. H. Haploinsufficiency of the mouse forkhead box f1
gene causes defects in gall bladder development. J. Biol. Chem. 277:
12369-12374, 2002.
96. BONE MORPHOGENETIC PROTEIN RECEPTOR, TYPE IA; BMPR1A (human only)
Howe, J. R., Sayed, M. G., Ahmed, A. F., Ringold, J., Larsen-Haidle, J.,
Merg, A., Mitros, F. A., Vaccaro, C. A., Petersen, G. M., Giardiello, F.
M., Tinley, S. T., Aaltonen, L. A., Lynch, H. T. The prevalence of MADH4
and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B,
and ACVR1 mutations. J. Med. Genet. 41: 484-491, 2004.
97. BONE MORPHOGENETIC PROTEIN RECEPTOR, TYPE IA; BMPR1A (mouse only)
Yoon, B. S., Ovchinnikov, D. A., Yoshii, I., Mishina, Y., Behringer, R.
R., Lyons, K. M. Bmpr1a and Bmpr1b have overlapping functions and are
essential for chondrogenesis in vivo. Proc. Nat. Acad. Sci. 102:
5062-5067, 2005.
98. BONE MORPHOGENETIC PROTEIN RECEPTOR, TYPE IB; BMPR1B
Lehmann, K., Seemann, P., Stricker, S., Sammar, M., Meyer, B., Suring,
K., Majewski, F., Tinschert, S., Grzeschik, K.-H., Muller, D., Knaus,
P., Nurnberg, P., Mundlos, S. Mutations in bone morphogenetic protein
receptor 1B cause brachydactyly type A2. Proc. Nat. Acad. Sci. 100:
12277-12282, 2003.
99. GHRELIN; GHRL (human)
Steinle, N. I., Pollin, T. I., O'Connell, J. R., Mitchell, B. D.,
Shuldiner, A. R. Variants in the ghrelin gene are associated with
metabolic syndrome in the old order Amish. J. Clin. Endocr. Metab. 90:
6672-6677, 2005.
100. GHRELIN; GHRL (mouse only)
Wortley, K. E., Anderson, K. D., Garcia, K., Murray, J. D., Malinova,
L., Liu, R., Moncrieffe, M., Thabet, K., Cox, H. J., Yancopoulos, G. D.,
Wiegand, S. J., Sleeman, M. W. Genetic deletion of ghrelin does not
decrease food intake but influences metabolic fuel preference. Proc.
Nat. Acad. Sci. 101: 8227-8232, 2004.
101. Leptin (mouse only)
Szczypka, M. S., Rainey, M. A., Palmiter, R. D. Dopamine is required for
hyperphagia in Lep(ob/ob) mice. Nature Genet. 25: 102-104, 2000.
102. Leptin (Human only)
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H.,
Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J.
A., Cheetham, C. H., Earley, A. R., Barnett, A. H., Prins, J. B.,
O'Rahilly, S. Congenital leptin deficiency is associated with severe
early-onset obesity in humans. Nature 387: 903-908, 1997.
103. Fibrillin ; Fbn1 (Human only)
Dietz, H. C., Cutting, G. R., Pyeritz, R. E., Maslen, C. L., Sakai, L.
Y., Corson, G. M., Puffenberger, E. G., Hamosh, A., Nanthakumar, E. J.,
Curristin, S. M., Stetten, G., Meyers, D. A., Francomano, C. A. Marfan
syndrome caused by a recurrent de novo missense mutation in the
fibrillin gene. Nature 352: 337-339, 1991.
104. Fibrillin ; Fbn1 (mouse only)
Pereira, L., Andrikopoulos, K., Tian, J., Lee, S. Y., Keene, D. R., Ono,
R., Reinhardt, D. P., Sakai, L. Y., Biery, N. J., Bunton, T., Dietz, H.
C., Ramirez, F. Targetting (sic) of the gene encoding fibrillin-1
recapitulates the vascular aspect of Marfan syndrome. Nature Genet. 17:
218-222, 1997.