Work Package 5 - a Genetically-Based Strategy to Identify New Targets in Ldl- C Metabolism

WORK PACKAGE 5 - A GENETICALLY-BASED STRATEGY TO IDENTIFY NEW TARGETS IN LDL- C METABOLISM

Task 3 : Functional characterization of new FHBL/ADH genes

Méryl Roudaut Amandine Caillaud Karim SI-TAYEB

Unité Inserm UMR 1087-CNRS UMR 6291

Transatlantic Network of Excellence 2014-2019 WORK PACKAGE 5 - A GENETICALLY-BASED STRATEGY TO IDENTIFY NEW TARGETS IN LDL- C METABOLISM

Task 3 : Functional characterization of new FHBL/ADH genes Nouvelle cible FHBL UCell hypochol propositus’ sister (44386)

Microscopie optique

Native Ucell in culture UCell en cours de reprogrammation hiPS hypochol propositus (43899)

Characterisation : Immunofluorescence

OCT4 Tra1-60 Dapi Merge

Clone 5 Clone

Clone 7 Clone hiPS hypochol propositus (43899)

Characterisation : flow cytometry

Tra1-60 SSEA3 SSEA4

Clone 5 Clone

Clone 7 Clone Work in progress…

Propositus’ sister: - Clone picking - early characterization

Propositus : - further characterization - hepatocyte differentiation (ongoing)

What we need now?

Hints from the genetic team to focus our functionnal exploration

Developing a 3D model of Human iPS Cell-derived Hepatocytes

Méryl Roudaut

Jun, 29th 2017 Summary

First part : generality Summary

First part : generality

Second part : first differentiation step Summary

First part : generality

Second part : first differentiation step

Third part : second differentiation step Summary

First part : generality

Second part : first differentiation step

Third part : second differentiation step

Conclusion 3D gels and microenvironnement

3D compared to 2D culture : hepatic differentiation of UhiPS cells enhanced the expression of genes involved in cholesterol metabolism regulation

Scaffolds are formed by crosslinking of Hyaluronic Acid with ADH (Adipic Acid Di-Hydrazide) to form reticulated chains that can be functionnalized.

Institut du thorax - Human iPS Cell-derived Hepatocytes 2D protocol

Days 0 2 5

Tissus ENDODERM

Cytokins Activin A Activin A FGF2 BMP4

Institut du thorax - Human iPS Cell-derived Hepatocytes 2D protocol

Days 0 2 5 10 15

Tissus ENDODERM HEPATIC ENDODERM HEPATIC PROGENITOR

Cytokins Activin A Activin A FGF2 HGF FGF2 BMP4 BMP4

Institut du thorax - Human iPS Cell-derived Hepatocytes 2D protocol

Days 0 2 5 10 15 20

Tissus ENDODERM HEPATIC ENDODERM HEPATIC PROGENITOR HEPATOCYTES

Cytokins Activin A Activin A FGF2 HGF OSM FGF2 BMP4 BMP4

Second part : first differentiation step Experimentation plan

Optimisation of seeding and the beginning of differentiation

Days 0 2 5

Tissus ENDODERM

Cytokins Activin A Activin A FGF2 BMP4 Experimentation plan

Optimisation of seeding and the beginning of differentiation

Seeding volume (ul) 10 20 Experimentation plan

Optimisation of seeding and the beginning of differentiation

Seeding volume (ul) 10 20

Cell number 50 000 100 000 200 000 … Experimentation plan

Optimisation of seeding and the beginning of differentiation

Seeding volume (ul) 10 20

Cell number 50 000 100 000 200 000 … … … Control condition Cytokins concentration (D 0) (compared to 2D)

D 0-2 X 1 X 2 X 2 X 5 Experimentation plan

Optimisation of seeding and the beginning of differentiation

Seeding volume (ul) 10 20

Cell number 50 000 100 000 200 000 … … … Control condition Cytokins concentration (D 0) (compared to 2D)

D 0-2 X 1 X 2 X 2 X 5

D 2-5 X 1 X 5 X 10 X 10 (A) (B) (C) (D) Results

For the first step : 30 different conditions + controls conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes

OCT4

NANOG

SOX2 Results

For the first step : 30 different conditions + controls conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes Endoderm genes

OCT4 FOXA2

NANOG SOX17

SOX2 Results

For the first step : 30 different conditions + controls conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes Endoderm genes Hepatics progenitor genes

OCT4 FOXA2 HNF4

NANOG SOX17

SOX2 Results

For the first step : 30 different conditions + controls conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes Endoderm genes Hepatics progenitor genes

OCT4 FOXA2 HNF4

NANOG SOX17

SOX2

Best condition : 10 100 000 X 2 X 10 (C) Results

Best condition OCT4

Control condition Results

Best condition NANOG

Control condition Results

Best condition SOX2

Control condition Results

FOXA2 Best condition

Control condition Results

SOX17 Best condition

Control condition Results

HNF4

Best condition

Control condition Results

Importance of the ARN quantity and quality

Best condition Third part : second differentiation step Institut du thorax - Human iPS Cell-derived Hepatocytes 3D protocol

Seeding volume 10

Cell number 100 000

Days 0 2 5

Tissus ENDODERM

Cytokins Activin A Activin A FGF2 BMP4 X 2 X 10

Institut du thorax - Human iPS Cell-derived Hepatocytes 3D protocol

Seeding volume 10

Cell number 100 000

Days 0 2 5 10

Tissus ENDODERM HEPATIC ENDODERM HEPATIC PROGENITOR

Cytokins Activin A Activin A FGF2 FGF2 BMP4 BMP4 X 2 X 10 X ?

Institut du thorax - Human iPS Cell-derived Hepatocytes 3D protocol

FGF2

EGF PDGF RAC1 NKD1 WNT PATHWAY VEGF

Institut du thorax - Human iPS Cell-derived Hepatocytes 3D protocol

Seeding volume 10

Cell number 100 000

Days 0 2 5 10

Tissus ENDODERM HEPATIC ENDODERM

Cytokins Activin A Activin A FGF2 FGF2 BMP4 BMP4 Synergy with FGF2 X 2 X 10 X ? + VEGF or PDGF or EGF

Experimentation plan

Optimisation of hepatic progenitor differentiation

Seeding volume (ul) 10 Cell number 100 000

Cytokins concentration (compared to 2D)

D 0-2 X 2

D 2-5 X 10 Experimentation plan

Optimisation of hepatic progenitor differentiation

Seeding volume (ul) 10 Cell number 100 000

Cytokins concentration (compared to 2D)

D 0-2 X 2

D 2-5 X 10

D 5-10 X 5 X 10 Experimentation plan

Optimisation of hepatic progenitor differentiation

Seeding volume (ul) 10 Cell number 100 000

Cytokins concentration (compared to 2D)

D 0-2 X 2

D 2-5 X 10

D 5-10 (E) X 5 (F) X 10

… VEGF PDGF EGF Experimentation plan

Optimisation of hepatic progenitor differentiation

D 5-10 (E) X 5 (F) X 10

… VEGF PDGF EGF

Same to VEGF … C1 C2 C1 Experimentation plan

Optimisation of hepatic progenitor differentiation

D 5-10 (E) X 5 (F) X 10

… VEGF PDGF EGF

Same to VEGF … C1 C2 C1

… … D F T

D : Day 5 to 8

F : Day 8 to 10

T : Day 5 to 10 Results

For the second step : 32 different conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes

OCT4

NANOG

SOX2 Results

For the second step : 32 different conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes Endoderm genes

OCT4 FOXA2

NANOG

SOX2 Results

For the second step : 32 different conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes Endoderm genes Hepatics progenitor genes OCT4 FOXA2 HNF4

NANOG HNF1b

SOX2 FOXA3 TBX3

HHEX

PPARA Results

For the second step : 32 different conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes Endoderm genes Hepatics progenitor Hepatocytes genes genes OCT4 FOXA2 HNF4 Albumine

NANOG HNF1b AFP

SOX2 FOXA3 TBX3

HHEX

PPARA Results

For the second step : 32 different conditions

Only genes expression are seen in RT qPCR :

Pluripotence genes Endoderm genes Hepatics progenitor Hepatocytes genes genes OCT4 FOXA2 HNF4 Albumine

NANOG HNF1b AFP

SOX2 FOXA3 TBX3

HHEX

(E) PPARA Best condition : X 5 VEGF C2 T E VEGF T Results Results Results Results Results Results Conclusion

Seeding volume 10

Cell number 100 000

Days 0 2 5

Tissus ENDODERM

Cytokins Activin A Activin A FGF2 BMP4 X 2 X 10

Conclusion

Seeding volume 10

Cell number 100 000

Days 0 2 5 8 10

Tissus ENDODERM HEPATIC ENDODERM

Cytokins Activin A Activin A FGF2 FGF2 BMP4 BMP4 X 2 X 10 X 5

+ VEGF C2

Conclusion

Seeding volume 10

Cell number 100 000

Days 0 2 5 8 10

Tissus ENDODERM HEPATIC ENDODERM

Cytokins Activin A Activin A FGF2 FGF2 BMP4 BMP4 X 2 X 10 X 5

+ VEGF C2

Conclusion

I am here

Days 0 2 5 8 10 15 20

Tissus ENDODERM HEPATIC ENDODERM HEPATIC PROGENITOR HEPATOCYTE Conclusion

Seeding volume 10

Cell number 100 000

Days 0 2 5 8 10 15 20

Tissus ENDODERM HEPATIC ENDODERM HEPATIC PROGENITOR HEPATOCYTES

Cytokins Activin A Activin A FGF2 HGF OSM FGF2 BMP4 BMP4 X 2 X 10 X 5 X ? X ?

+ VEGF C2

Conclusion

Days 20

Tissus HEPATOCYTE

December 2017 Validation Patenting Thanks for your attention

Any questions ?

Hypochol : état des lieux juin 2017 Le recrutement :

• 36 propositus Hypochol confirmés et prélevés pour la génétique • 4 avec des RDV prévus cet été • 10 en attente de prise de RDV

• Nouveau screening / base biologie du CHU de Nantes • Démarche prospective pour les CES • Bioliance : courrier séparé du bilan en prospectif et en rétrospectif en fin de validation

identitée Biologie mutatio N° N° sex nv LDL HDL chol trigly N° LD date de naissance envoi Diag n Rendu date bilan bio famille intégralis e g/L g/L tot g/L g/L connue 42578 42578 LD000M 09/12/1945 ? 04/12/2012 0,16 0,46 1,12 2,55 43899 43899 voir faF 03/05/1958 03/2017, absenceL 24/06/2014 0,51 0,73 1,33 0,44 44216 44216 LD000F 14/07/1967 à Lille,03/E - ; PCSK9 - 03/12/1014 0,21 0,84 1,09 0,19 44216 54935 LD002F 25/11/1965 12/09/2011 0,1 1,08 1,3 0,3 44216 54998 LD002F 09/06/1997 10/05/2017 1,08 0,64 1,83 0,55 Les résultats 45269 45269 LD000M 14/04/1943Lyon 3/17 01/04/2015 0,74 0,57 1,44 0,67 45420 45420 LD000M 27/04/1979Lyon 5/17 15/11/2014 0,38 0,35 0,87 0,72 / Lyon 45429 45429 LD000M 25/03/1977 non? 27/01/2014 0,46 0,99 1,64 0,97 47002 47002 LD000F 19/03/1988 7/15, résultats ? 01/07/2015 0,49 0,53 1,09 0,36 47260 47260 LD000M 10/05/1972 ats ? ; envoi diag Lyon 06/1 16/04/2015 0,51 0,37 1,38 2,49 47260 47511 LD000F 21/07/1970 23/09/2015 1,32 0,45 2,04 1,35 47490 47490 LD000F 18/09/1994on, 11/20Apo B à faire 28/10/2015 0,49 0,74 1,28 0,23 48554 48554 LD001F 25/02/1987 Lille, 1/2016, résultats ? 05/01/2016 0,31 0,65 1,16 1 51460 51460 LD001F 07/06/1995 /2016, Lyabsence 4/05/2017 26/10/2016 0,21 0,95 1,25 0,45 51729 51729 LD001F 15/12/1991 /2016, Lyabsence 5/5/17 pa 16/11/2016 0,58 0,69 1,4 0,63 52072 52072 LD001F 17/04/1976 /2016, Lyabsence 15/06/17 p14/11/2016 0,64 0,93 1,64 0,32 52103 52103 LD001M 17/01/1952 /2016, LyApo B + e 7/6/17 pa07/06/2017 0,36 1,21 1,66 0,41 52172 52172 LD001F 05/01/1983 /2016, LyApo B + à faire 21/10/2016 0,22 0,86 1,12 0,21 52269 52269 LD001F 25/03/1973 /2016, Lyabsence à faire 07/12/2016 0,58 0,78 1,5 0,66 52576 52576 LD001M 17/11/196902/ 17 lyon 07/02/2017 0,54 0,52 1,24 0,93 52613 52613 LD001F 22/09/199102/ 17 lyon 08/02/2017 0,52 0,68 1,34 0,72 53300 53300 LD001F 04/06/1994 ars 17 lyon 08/02/2017 0,62 0,53 1,25 0,49 54061 54061 LD001F 20/12/1986 ars 17 lyon 07/03/2017 0,42 1,15 1,7 0,61 54753 54753 LD002F 15/04/1991vril 17 lyon 04/04/2017 0,33 0,62 1,16 1,04 55743 55743 LD002F 01/03/1998 juin 2017 lyon 06/06/2017 0,41 0,62 1,29 1,29 55988 55988 LD002F 25/02/1989 juin 2017 lyon 07/06/2017 0,53 0,89 1,62 0,89 56139 56139 M 29/12/1995 juin 2017 lyon 27/06/2017 0,42 0,84 1,34 0,39 Le dépistage familial :

• 11 familles dépistées ou en cours de dépistage (bilan biologique et génétique) • 64 apparentés prélevés en génétique • Attente des rendus pour lancer le dépistage dans les nouvelles familles (4 déjà fait avec les résultats de Lyon, 3 prévu ou à prévoir)

Famille 47490

? ?

2/2/1935 DCD jeune LDL 1.03g/l DCD à 60ans pas d'enfant sous pravastatine diabète a donné son corps à la science

? ? ? ? ? ? ?

(Lebot) 10/1/1963 5/8/1964 LDL 1.39 LDL 0.43 LDL 1.11g/l ? ? ? ?

? ? ? ? ? ?

? ? ? ? ? ? ? ? 47490 Nouvelle mutation Apo B exon 3: 18/9/1994 23/8/1989 13/1/2003 5 LDL 0.40g/l LDL 0.78g/l L délétion hétérozygote Famille 51460

? ? ? ? ? ? ? ?

DC tardif DC tardif DCD à 94 /95 ans cousine *

? ? ? ? Rendu fait le 24/05/17 tx choles bas K pancréas ! Aucune mutation cousine * retrouvée

? ? ? ? ? ? ?

7/4/1965 23/1/1964

? ?

27/12/1991 4/2/1999 7/6/1995

Famille 51729 ? ?

DCD à 83 ans parkison

? ? ?

? - 1/ 1/ 1984 1/ 9/ 1935 DCD depuis 20ans adopt é ? f ille unique TTT choles K poumon peu de cont act

? ? ? ? 54796 54795 1/ 1/ 1973 1/ 1/ 1961 24/ 7/ 1963 28/ 3/ 1957 pb rein, colique néph op aucun cont act LDL 1. 03g/ l LDL 0. 77g/ l TTT pour le choles pas d'enf ant pas d'enf ant sous simvastatine Rendu fait le 5/05/17 ! Pas de mutation identifiée

? ? 51729 15/ 12/ 1991 24/ 10/ 1985 14/ 7/ 1988 LDL 0. 58g/ l absence mut at ion Famille 52072

? ? ? ?

? - 1/1/ 2002 DCD à 68 ans suicide 98 ans K des os k sein

? ? ? ? ? ? ? ?

30/11/ 1952 4/ 4/ 1955 peu de contact peu de contact peu de contact peu de contact f âché mais possible mais possible mais possible mais possible

Rendu fait le 15/06/17 ? ? ! pas de mutation 52072 8/ 3/ 1979 11/7/ 1983 17/4/ 1976 identifiée LDL bas ? LDL 0.64g/ l Famille 52103

? DCD jeune DCD jeune

? ? ? ? ? ? ?

23/5/1920 - 1980 27/6/1923 - 1979 K prostate K poumon ? insf rénal, EP, phlébite suicide AVC, HTA HTA DCD à 31 ans

52103 ? ? ? ? ? ? ? 17/1/1952 ? Nouvelle mutation Apo B, LDL 0.36g/L ségrégation familiale en peu de contactpeu de contactpeu de contact Rendu fait pas de contact cours (exon 6 : variation le 7/06/17 hétérozygote bénigne et 54798 54799 mutation hétérozygote 14/3/1976 20/10/1978 LDL 0.15g/L CT 1.03g/L avec codon stop)

? ? ? Famille 52172

? ?

DCD à 73 ans DCD à 92 ans ? 52446 Rendu à faire 28/8/1929 Nouvelle mutation LDL 0.58 DCD à 85 ans , Alzheimer Apo B exon 4 : ? substitution non sens 52445 hétérozygote 27/9/1951 19/8/1954 pas de contact LDL 0.56g/L origine espagnole

52172 5/1/1983 LDL 0.22g/L Famille 52269

? ?

DCD en 2006 DCD jeune DCD à 93ans 93 ans à 80ans LDL 0.85 et 2.19g/l sous traitement Rendu programmé pour le 5/07/17 ? ? ! Aucune mutation

1/4/1949retrouvée DCD DCD crise cardiaqueLDL 1.25g/l pas d'enfant pb hygiène de vie

? ? ? 52269 18/2/1969 25/3/1973 LDL 1.37g/l LDL normal pas d'enfant LDL 0.43g/l Recrutement de Lyon :

• Propositus recrutés à Lyon : • fiche Intégralis créée et remplie de façon anomyme (initiale, DDN + N° anonymisation à définir) par Harout ILIOZER, y compris la partie cst, sauf pour le Biocol (vérif à Nantes à réception des prélèvements • 2 tubes de sang pour le diag à Lyon • 2 tubes de sang pour la recherche à l’INSERM Nantes avec consentement Biocol anomymisé + non anonymisé dans une enveloppe Merci de votre attention

Direction de la Recherche • Département partenariat et innovation Immeuble Deurbroucq • 5 allée de l’île Gloriette • 44093 Nantes Cedex 01 Mail : [email protected] www.rhuchopin.fr

Hypobetalipoproteinemia Search for the genetic origin

Unité Inserm UMR 1087-CNRS UMR 6291

2017 May 5th Pilot Study – Analysis of Candidate Genes in Eight HBL patients • Sequencing of 10 candidate genes (HaloPlex – Agilent Technologies) APOB, PCSK9, ANGPTL3, MTTP, SAR1B

APOE, CETP, LDLR, MYLIP , SORT1

• Identification of 5 heterozygous mutations among 5 patients APOB p. Gln845*, pGln2571*, p.Cys2933*, p.Ser3718*

PCSK9 p.Asp175Serfs* or p.Asp175Asn

(Rimbert et al., Atherosclerosis 2016)

• No disclosed variant in these candidate genes in 3 patients

HYPOCHOL : 2nd step Whole exome sequencing in family 43899

Variants identified in common in Family 43899

3 patients  8 variants

GENE CHROM POS REF ALT First ID SAMPLE

UNC45B 17 33513534 CTCA C LD00075, LD00095, LD00128 KRT19,KRT15 17 39680388 C CA LD00075, LD00095, LD00128 HSF5 17 56540165 C T rs141637268 LD00075, LD00095, LD00128 PASK,MTERFD2 2 242046049 C T rs148038387 LD00075, LD00095, LD00128 LOC100996335 22 21663552 G A rs62236681 LD00075, LD00095, LD00128 SPEF2 5 35694432 G T rs200903448 LD00075, LD00095, LD00128 PCDHA1,2,3,4,5,6,7,8 5 140221195 G C rs199713478 LD00075, LD00095, LD00128 CAMK2B 7 44269021 T TGGGCA LD00075, LD00095, LD00128

Variants identified in common in Family 43899

4 patients  3 variants

GENE CHROM POS REF ALT First ID SAMPLE

CCDC177 14 70039803 CGCGGCG C rs147747237 LD00075, LD00095, LD00128, LD00081 LOC388282,KIFC3 16 57847634 A ATGCAGGTG rs56192221 LD00075, LD00095, LD00128, LD00081 LOC100996335 22 21663537 T A LD00075, LD00095, LD00128, LD00081 Genotyping – Identity by Descent (IBD) (Axiom® Precision Medicine Research Array - PMRA, Affymetrix)

Shared regions : chrom start end 3 148633507 172089235 5 95594513 106375215 7 45221685 49633802 Family 43899 : WES / IBD

CHROM POS GENE

17 33513534 UNC45B 17 39680388 KRT19,KRT15 17 56540165 HSF5 2 242046049 PASK,MTERFD2 WES 3 p. 22 21663552 LOC100996335 5 35694432 SPEF2 5 140221195 PCDHA1,2,3,4,5,6,7,8 7 44269021 CAMK2B

14 70039803 CCDC177 4 p. 16 57847634 LOC388282,KIFC3 22 21663537 LOC100996335

Shared regions : IBD chrom start end 3 148633507 172089235 5 95594513 106375215 7 45221685 49633802 Genotyping – Identity by Descent (IBD)

Shared regions : chrom start end 3 148633507 172156872 5 1938681 36465332 5 95090923 106789764 7 44327445 49633802 12 119306069 128579558 Shared region on Chr3 GYG1 IGSF10 TIPARP SMC4 MIR551B TNIK HLTF MIR5186 LINC00886 MIR15B EGFEM1P Y_RNA HLTF-AS1 MIR548H2 PA2G4P4 MIR16-2 EVI1 PLD1 HPS3 AADACL2 AK094480 DM119508 MECOM TMEM212 CP LOC201651 LEKR1 SMC4 DD413694 FNDC3B TM4SF18 AADAC LINC00880 TRIM59 TERC GHSR TM4SF1 SUCNR1 LINC00881 U7 ACTRT3 GU289929 WWTR1 MBNL1-AS1 CCNL1 KPNA4 TRNA_Val U6 MBNL1-AS1 VEPH1 SCARNA7 MYNN AK309441 MBNL1 PTX3 BC125159 LRRC34 WWTR1-AS1 TMEM14E Mir_584 Mir_562 LRRIQ4 COMMD2 MBNL1 C3orf55 ARL14 LRRC31 ANKUB1 P2RY1 7SK PPM1L SAMD7 RNF13 RAP2B SHOX2 AK055323 LOC100128164 PFN2 AK092619 RSRC1 B3GALNT1 SEC62 LOC646903 C3orf79 AK097794 NMD3 GPR160 TSC22D2 ARHGEF26-AS1 MLF1 SPTSSB PHC3 SERP1 ARHGEF26 GFM1 LOC101243545 AY940074 EIF2A DHX36 LXN OTOL1 PHC3 BC039424 GPR149 RARRES1 BC073807 BC131773 SELT MME AY070437 CT64 PRKCI FAM194A BC037382 MFSD1 SI JA611273 SIAH2 LOC100507537 IQCJ SLITRK3 PRKCI CLRN1-AS1 PLCH1 IQCJ-SCHIP1 BCHE SKIL CLRN1 C3orf33 SCHIP1 7SK CLDN11 CLRN1-AS1 SLC33A1 MIR3919 ZBBX SLC7A14 MED12L AK130481 IQCJ-SCHIP1 SERPINI2 BC039437 5S_rRNA GMPS U2 WDR49 RPL22L1 Chr3 GPR171 KCNAB1 SCHIP1 PDCD10 EIF5A2 KCNAB1-AS2 AK097161 SERPINI1 U1 148,633,507-172,215,332 P2RY14 GPR87 KCNAB1-AS1 IL12A LOC646168 SLC2A2 (23,581,826 bp) P2RY13 SSR3 C3orf80 GOLIM4 TNIK MED12L TIPARP-AS1 IFT80 EGFEM1P MIR569 IBD: new shared region on chromosome 5

C5orf38 FAM105B MTMR12 IRX1 ANKH ZFR BC034630 MIR4637 SUB1 AK094462 FBXL7 NPR3 ADAMTS16 Mir_887 5S_rRNA KIAA0947 MARCH11 TARS FLJ33360 BC043001 ADAMTS12 MED10 ZNF622 U6 UBE2QL1 FAM134B RXFP3 NSUN2 MYO10 SLC45A2 SRD5A1 BASP1 AMACR PAPD7 7SK C1QTNF3 MIR4278 BC028204 DQ587763 MIR4454 CDH18 DQ571461 LOC442132 AK093362 DQ578105 ADCY2 GUSBP1 DQ598168 C5orf49 DQ596041 RAI14 FASTKD3 DQ591060 5S_rRNA MTRR BC038535 TTC23L MIR4458 CDH12 RAD1 BC032891 PMCHL1 BRIX1 SEMA5A PRDM9 DNAJC21 MIR4636 AX747383 AGXT2 SNORD123 Y_RNA Mir_548 TAS2R1 CDH10 PRLR 5S_rRNA TRNA_Lys SPFE2 FAM173B CDH9 IL7R CCT5 LSP1P3 CAPSL CMBL AK098570 UGT3A2 MARCH6 CDH6 AK094621 ROPN1L DROSHA LMBRD2 Chr5 ANKRD33B Mir_562 MIR580 DAP C5orf22 SKP2 1,938,681-36,465,332 CTNND2 PDZD2 NADKD1 CT49 MIR4279 RANBP3L (34,526,652 bp) DNAH5 PDZD2 TRIO GOLPH3 FAM105A IBD: shared region on chromosome 5 (1,938,681-36,465,332) 1 C5orf38 chromosome 5 open reading frame 38 (C5orf38), mRNA. IRX1 iroquois homeobox 1 (IRX1), mRNA. BC034630 cDNA clone IMAGE:4839194. AK094462 cDNA FLJ37143 fis, clone BRACE2024222. ADAMTS16 ADAM metallopeptidase with thrombospondin type 1 motif, 16 (ADAMTS16), mRNA. KIAA0947 KIAA0947 (KIAA0947), mRNA. FLJ33360 FLJ33360 protein (FLJ33360), non-coding RNA. MED10 mediator complex subunit 10 (MED10), mRNA. UBE2QL1 ubiquitin-conjugating enzyme E2Q family-like 1 (UBE2QL1), mRNA. NSUN2 NOP2/Sun RNA methyltransferase family, member 2 (NSUN2), transcript variant 2, mRNA. SRD5A1 steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1), mRNA. PAPD7 PAP associated domain containing 7 (PAPD7), transcript variant 2, mRNA. MIR4278 microRNA 4278 (MIR4278), microRNA. MIR4454 microRNA 4454 (MIR4454), microRNA. LOC442132 golgin A6 family-like 1 pseudogene (LOC442132), non-coding RNA. ADCY2 adenylate cyclase 2 (brain) (ADCY2), mRNA. C5orf49 chromosome 5 open reading frame 49 (C5orf49), mRNA. FASTKD3 FAST kinase domains 3 (FASTKD3), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA. MTRR 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), transcript variant 2, mRNA. MIR4458 microRNA 4458 (MIR4458), microRNA. BC032891 cDNA clone IMAGE:5259428. SEMA5A sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cy MIR4636 microRNA 4636 (MIR4636), microRNA. SNORD123 small nucleolar RNA, C/D box 123 (SNORD123), small nucleolar RNA. TAS2R1 taste receptor, type 2, member 1 (TAS2R1), mRNA. 5S_rRNA Rfam model RF00001 hit found at contig region AC091838.2/58847-58741 FAM173B family with sequence similarity 173, member B (FAM173B), transcript variant 6, non-coding RNA. CCT5 chaperonin containing TCP1, subunit 5 (epsilon) (CCT5), mRNA. CMBL carboxymethylenebutenolidase homolog (Pseudomonas) (CMBL), mRNA. MARCH6 membrane-associated ring finger (C3HC4) 6, E3 ubiquitin protein ligase (MARCH6), transcript variant 3, mRNA. ROPN1L rhophilin associated tail protein 1-like (ROPN1L), transcript variant 2, mRNA. ANKRD33B ankyrin repeat domain 33B (ANKRD33B), mRNA. DAP death-associated protein (DAP), mRNA. 5 CTNND2 catenin (cadherin-associated protein), delta 2 (CTNND2), mRNA. CT49 cancer/testis antigen 49 (non-protein coding) (CT49), non-coding RNA. DNAH5 dynein, axonemal, heavy chain 5 (DNAH5), mRNA. TRIO trio Rho guanine nucleotide exchange factor (TRIO), mRNA. FAM105A family with sequence similarity 105, member A (FAM105A), mRNA. IBD: shared region on chromosome 5 (1,938,681-36,465,332) 2 FAM105B family with sequence similarity 105, member B (FAM105B), mRNA. ANKH ankylosis, progressive homolog (mouse) (ANKH), mRNA. MIR4637 microRNA 4637 (MIR4637), microRNA. FBXL7 F-box and leucine-rich repeat protein 7 (FBXL7), transcript variant 1, mRNA. Mir_887 Rfam model RF01035 hit found at contig region AC091872.3/26278-26356 MARCH11 membrane-associated ring finger (C3HC4) 11 (MARCH11), mRNA. BC043001 hypothetical gene supported by BC043001, mRNA (cDNA clone IMAGE:5297432). ZNF622 zinc finger protein 622 (ZNF622), mRNA. FAM134B family with sequence similarity 134, member B (FAM134B), transcript variant 2, mRNA. MYO10 myosin X (MYO10), mRNA. BASP1 brain abundant, membrane attached signal protein 1 (BASP1), transcript variant 2, mRNA. 7SK Rfam model RF00100 hit found at contig region AC026785.4/34925-34586 BC028204 cDNA clone IMAGE:5201079. CDH18 cadherin 18, type 2 (CDH18), transcript variant 2, mRNA. AK093362 cDNA FLJ36043 fis, clone TESTI2017582. GUSBP1 glucuronidase, beta pseudogene 1 (GUSBP1), transcript variant 3, non-coding RNA. DQ596041 piRNA piR-33322, complete sequence. DQ591060 piRNA piR-42794, complete sequence. BC038535 clone IMAGE:5171606, mRNA. CDH12 cadherin 12, type 2 (N-cadherin 2) (CDH12), mRNA. PMCHL1 pro-melanin-concentrating hormone-like 1, pseudogene (PMCHL1), non-coding RNA. PRDM9 PR domain containing 9 (PRDM9), mRNA. AX747383 cDNA FLJ34836 fis, clone NT2NE2010400. Y_RNA Rfam model RF00019 hit found at contig region AC026784.5/68998-69099 CDH10 cadherin 10, type 2 (T2-cadherin) (CDH10), mRNA. TRNA_Lys transfer RNA Lys (anticodon CTT) CDH9 cadherin 9, type 2 (T1-cadherin) (CDH9), mRNA. LSP1P3 lymphocyte-specific protein 1 pseudogene 3 (LSP1P3), non-coding RNA. AK098570 cDNA FLJ25704 fis, clone TST04756. CDH6 cadherin 6, type 2, K-cadherin (fetal kidney) (CDH6), mRNA. DROSHA drosha, ribonuclease type III (DROSHA), transcript variant 2, mRNA. Mir_562 Rfam model RF00998 hit found at contig region AC008768.8/25577-25677 C5orf22 chromosome 5 open reading frame 22 (C5orf22), mRNA. 5 PDZD2 PDZ domain containing 2 (PDZD2), mRNA. MIR4279 microRNA 4279 (MIR4279), microRNA. PDZD2 PDZ domain containing 2 (PDZD2), mRNA. GOLPH3 golgi phosphoprotein 3 (coat-protein) (GOLPH3), mRNA. IBD: shared region on chromosome 5 (1,938,681-36,465,332) 3

MTMR12 myotubularin related protein 12 (MTMR12), mRNA. ZFR zinc finger RNA binding protein (ZFR), mRNA. SUB1 SUB1 homolog (S. cerevisiae) (SUB1), mRNA. NPR3 natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C) (NPR3), transcript varian 5S_rRNA Rfam model RF00001 hit found at contig region AC025472.4/33041-32936 TARS threonyl-tRNA synthetase (TARS), transcript variant 6, non-coding RNA. ADAMTS12 ADAM metallopeptidase with thrombospondin type 1 motif, 12 (ADAMTS12), mRNA. U6 Rfam model RF00026 hit found at contig region AC139777.3/94180-94074 RXFP3 relaxin/insulin-like family peptide receptor 3 (RXFP3), mRNA. SLC45A2 solute carrier family 45, member 2 (SLC45A2), transcript variant 2, mRNA. AMACR alpha-methylacyl-CoA racemase (AMACR), nuclear gene encoding mitochondrial protein, transcript variant 3, m C1QTNF3 C1q and tumor necrosis factor related protein 3 (C1QTNF3), transcript variant 2, mRNA. DQ587763 piRNA piR-54875, complete sequence. DQ571461 piRNA piR-30261, complete sequence. DQ578105 piRNA piR-46217, complete sequence. DQ598168 piRNA piR-57410, complete sequence. RAI14 retinoic acid induced 14 (RAI14), transcript variant 6, mRNA. 5S_rRNA Rfam model RF00001 hit found at contig region AC026801.7/44417-44520 TTC23L tetratricopeptide repeat domain 23-like (TTC23L), mRNA. RAD1 RAD1 homolog (S. pombe) (RAD1), transcript variant 1, mRNA. BRIX1 BRX1, biogenesis of ribosomes, homolog (S. cerevisiae) (BRIX1), mRNA. DNAJC21 DnaJ (Hsp40) homolog, subfamily C, member 21 (DNAJC21), transcript variant 2, mRNA. AGXT2 alanine--glyoxylate aminotransferase 2 (AGXT2), nuclear gene encoding mitochondrial protein, mRNA. Mir_548 Rfam model RF01061 hit found at contig region AC010368.4/107937-107854 PRLR prolactin receptor (PRLR), transcript variant 6, mRNA. SPEF2 sperm flagellar 2, transcript variant 2, mRNA IL7R interleukin 7 receptor (IL7R), mRNA. CAPSL calcyphosine-like (CAPSL), transcript variant 2, mRNA. UGT3A2 UDP glycosyltransferase 3 family, polypeptide A2 (UGT3A2), transcript variant 2, mRNA. AK094621 cDNA FLJ37302 fis, clone BRAMY2016009. LMBRD2 LMBR1 domain containing 2 (LMBRD2), mRNA. MIR580 microRNA 580 (MIR580), microRNA. 5 SKP2 S-phase kinase-associated protein 2, E3 ubiquitin protein ligase (SKP2), transcript variant 3, mRNA. NADKD1 NAD kinase domain containing 1 (NADKD1), transcript variant 2, mRNA. RANBP3L RAN binding protein 3-like (RANBP3L), transcript variant 2, mRNA. Cosegregation Analysis in Family 43899

 No cosegregation IBD: shared region on Chromosome 5

RHOBTB3 Rho-related BTB domain containing 3 (RHOBTB3), mRNA. GLRX glutaredoxin (thioltransferase) (GLRX), transcript variant 4, mRNA. C5orf27 chromosome 5 open reading frame 27 (C5orf27), non-coding RNA. ELL2 elongation factor, RNA polymerase II, 2 (ELL2), mRNA. MIR583 microRNA 583 (MIR583), microRNA. PCSK1 proprotein convertase subtilisin/kexin type 1 (PCSK1), transcript variant 3, mRNA. CAST calpastatin (CAST), transcript variant 11, mRNA. ERAP1 endoplasmic reticulum aminopeptidase 1 (ERAP1), transcript variant 3, mRNA. AK094985 cDNA FLJ37666 fis, clone BRHIP2011576. ERAP2 endoplasmic reticulum aminopeptidase 2 (ERAP2), transcript variant 2, mRNA. LNPEP leucyl/cystinyl aminopeptidase (LNPEP), transcript variant 2, mRNA. BC107094 cDNA clone IMAGE:40015599. LIX1 Lix1 homolog (chicken) (LIX1), mRNA. RIOK2 RIO kinase 2 (RIOK2), transcript variant 2, mRNA. HM358988 clone Hep3-19 actin-like mRNA, partial sequence. RGMB RGM domain family, member B (RGMB), mRNA. CHD1 chromodomain helicase DNA binding protein 1 (CHD1), mRNA. U6 Rfam model RF00026 hit found at contig region AC022121.6/108378-108480 DQ596041 piRNA piR-33322, complete sequence. DQ591060 piRNA piR-42794, complete sequence. JB137812 WO 2011019074-A/23: Nucleic acid for controlling fibrillization of cells or tissues. LOC100133050 glucuronidase, beta pseudogene (LOC100133050), non-coding RNA. DQ574682 piRNA piR-42794, complete sequence. DQ596042 piRNA piR-33322, complete sequence. DQ583509 piRNA piR-40764, complete sequence. FAM174A family with sequence similarity 174, member A (FAM174A), mRNA. ST8SIA4 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 (ST8SIA4), transcript variant 2, mRNA. SLCO4C1 solute carrier organic anion transporter family, member 4C1 (SLCO4C1), mRNA. SLCO6A1 solute carrier organic anion transporter family, member 6A1 (SLCO6A1), mRNA. AX747345 cDNA FLJ34759 fis, clone NT2NE2001874. PAM peptidylglycine alpha-amidating monooxygenase (PAM), transcript variant 5, mRNA. Chr5 GIN1 gypsy retrotransposon integrase 1 (GIN1), mRNA. 95,090,923-106,789,764 / PPIP5K2 diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2), transcript variant 2, mRNA. C5orf30 chromosome 5 open reading frame 30 (C5orf30), mRNA. 95,594,513-106,375,215 NUDT12 nudix (nucleoside diphosphate linked moiety X)-type motif 12 (NUDT12), mRNA. (11,698,842 / 10,780,703 bp) RAB9BP1 RAB9B, member RAS oncogene family pseudogene 1 (RAB9BP1), non-coding RNA. EFNA5 ephrin-A5 (EFNA5), mRNA. IBD: shared region on Chromosome 7 CAMK2B calcium/calmodulin-dependent protein kinase II beta (CAMK2B), transcript variant 8, mRNA. AX746562 cDNA FLJ33339 fis, clone BRACE2001779. NUDCD3 NudC domain containing 3 (NUDCD3), mRNA. NPC1L1 NPC1-like 1 (NPC1L1), transcript variant 2, mRNA. DDX56 DEAD (Asp-Glu-Ala-Asp) box helicase 56 (DDX56), transcript variant 2, mRNA. TMED4 transmembrane emp24 protein transport domain containing 4 (TMED4), mRNA. DQ574505 transmembrane emp24 protein transport domain containing 4, mRNA (cDNA clone IMAGE:3456382) OGDH oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide) (OGDH), nuclear gene encoding mitocho ZMIZ2 zinc finger, MIZ-type containing 2 (ZMIZ2), transcript variant 2, mRNA. BC008049 hypothetical protein DKFZp761I2123, mRNA (cDNA clone IMAGE:3631645), partial cds. PPIA peptidylprolyl isomerase A (cyclophilin A) (PPIA), mRNA. H2AFV H2A histone family, member V (H2AFV), transcript variant 5, mRNA. PURB purine-rich element binding protein B (PURB), mRNA. MYO1G myosin IG (MYO1G), mRNA. BC041623 cDNA clone IMAGE:3634379, partial cds. SNORA9 small nucleolar RNA, H/ACA box 9 (SNORA9), small nucleolar RNA. CCM2 cerebral cavernous malformation 2 (CCM2), transcript variant 4, mRNA. NACAD NAC alpha domain containing (NACAD), mRNA. TBRG4 transforming growth factor beta regulator 4 (TBRG4), transcript variant 4, mRNA. SNORA5C small nucleolar RNA, H/ACA box 5C (SNORA5C), small nucleolar RNA. SNORA5B small nucleolar RNA, H/ACA box 5B (SNORA5B), small nucleolar RNA. RAMP3 receptor (G protein-coupled) activity modifying protein 3 (RAMP3), mRNA. ADCY1 adenylate cyclase 1 (brain) (ADCY1), mRNA. BC015774 cDNA FLJ31470 fis, clone NT2NE2001432. DQ597235 piRNA piR-59592, complete sequence. IGFBP1 insulin-like growth factor binding protein 1 (IGFBP1), mRNA. IGFBP3 nsulin-like growth factor binding protein 3 (IGFBP3), transcript variant 2, mRNA. AK125311 cDNA FLJ43321 fis, clone NT2RI2027396. TNS3 tensin 3 (TNS3), mRNA. Chr7 C7orf65 chromosome 7 open reading frame 65 (C7orf65), mRNA. 44,327,445-49,633,802 PKD1L1 polycystic kidney disease 1 like 1 (PKD1L1), mRNA. C7orf69 chromosome 7 open reading frame 69 (C7orf69), mRNA. 45,221,685-49,633,802 PKD1L1 polycystic kidney disease 1 like 1 (PKD1L1), mRNA. (5,306,358 / 4,412,118 bp) HUS1 HUS1 checkpoint homolog (S. pombe) (HUS1), transcript variant 1, mRNA. SUN3 Sad1 and UNC84 domain containing 3 (SUN3), transcript variant 2, mRNA. C7orf57 chromosome 7 open reading frame 57 (C7orf57), transcript variant 3, mRNA. UPP1 uridine phosphorylase 1 (UPP1), transcript variant 2, mRNA. ABCA13 ATP-binding cassette, sub-family A (ABC1), member 13 (ABCA13), mRNA. AX746840 cDNA FLJ33876 fis, clone CTONG2007009. IBD: new shared region on chromosome 12 SRRM4 ANAPC5 HSPB8 RNF34 CCDC60 BC029038 AF086288 KDM2B TMEM233 ORAI1 7SK MORN3 PRKAB1 TMEM120B CIT AK123181 MIR1178 RHOF CCDC64 AK095700 RAB35 SETD1B AK130486 HPD GCN1L1 PSMD9 MIR4498 WDR66 RPLP0 JB023063 DL492076 BCL7A PXN MLXIP SIRT4 LRRC43 PLA2G1B IL31 MSI1 B3GNT4 COX6A1 DIABLO TRIAP1 VPS33A GATC CLIP1 SRSF9 TRNA_Asp DYNLL1 ZCCHC8 COQ5 SNORA9 RNF10 RSRC2 POP5 KNTC1 CABP1 HCAR1 MLEC HCAR2 UNC119B HCAR3 MIR4700 DENR Chr12 ACADS CCDC62 SPPL3 HIP1R 119,306,069-128,579,558 HNF1A VPS37B C12orf43 ABCB9 (9,273,490 bp) OASL OGFOD2 DQ570466 ARL6IP4 P2RX4 PITPNM2 CAMKK2 IBD: shared region on chromosome 12 (119,306,069-128,579,558) 1 SRRM4 serine/arginine repetitive matrix 4 (SRRM4), mRNA. HSPB8 heat shock 22kDa protein 8 (HSPB8), mRNA. CCDC60 coiled-coil domain containing 60 (CCDC60), mRNA. AF086288 full length insert cDNA clone ZD48A05. TMEM233 transmembrane protein 233 (TMEM233), mRNA. 7SK Rfam model RF00100 hit found at contig region AC002563.1/5416-5120 PRKAB1 protein kinase, AMP-activated, beta 1 non-catalytic subunit (PRKAB1), mRNA. CIT citron (rho-interacting, serine/threonine kinase 21) (CIT), transcript variant 2, mRNA. MIR1178 microRNA 1178 (MIR1178), microRNA. CCDC64 coiled-coil domain containing 64 (CCDC64), mRNA. RAB35 RAB35, member RAS oncogene family (RAB35), transcript variant 2, mRNA. AK130486 cDNA FLJ26976 fis, clone SLV02257. GCN1L1 GCN1 general control of amino-acid synthesis 1-like 1 (yeast) (GCN1L1), mRNA. MIR4498 microRNA 4498 (MIR4498), microRNA. RPLP0 ribosomal protein, large, P0 (RPLP0), transcript variant 2, mRNA. DL492076 Novel nucleic acids. PXN paxillin (PXN), transcript variant 4, mRNA. SIRT4 sirtuin 4 (SIRT4), mRNA. PLA2G1B phospholipase A2, group IB (pancreas) (PLA2G1B), mRNA. MSI1 musashi RNA-binding protein 1 (MSI1), mRNA. COX6A1 cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), nuclear gene encoding mitochondrial protein, mRNA. TRIAP1 TP53 regulated inhibitor of apoptosis 1 (TRIAP1), mRNA. GATC glutamyl-tRNA(Gln) amidotransferase, subunit C (GATC), transcript variant 1, mRNA. SRSF9 serine/arginine-rich splicing factor 9 (SRSF9), mRNA. DYNLL1 dynein, light chain, LC8-type 1 (DYNLL1), transcript variant 3, mRNA. COQ5 coenzyme Q5 homolog, methyltransferase (S. cerevisiae) (COQ5), nuclear gene encoding mitochondrial protein, mRNA. RNF10 ring finger protein 10 (RNF10), mRNA. POP5 processing of precursor 5, ribonuclease P/MRP subunit (S. cerevisiae) (POP5), transcript variant 3, mRNA. CABP1 calcium binding protein 1 (CABP1), transcript variant 3, mRNA. MLEC malectin (MLEC), mRNA. UNC119B unc-119 homolog B (C. elegans) (UNC119B), mRNA. MIR4700 microRNA 4700 (MIR4700), microRNA. ACADS acyl-CoA dehydrogenase, C-2 to C-3 short chain (ACADS), nuclear gene encoding mitochondrial protein, mRNA. SPPL3 signal peptide peptidase like 3 (SPPL3), mRNA. HNF1A HNF1 homeobox A (HNF1A), mRNA. 12 C12orf43 chromosome 12 open reading frame 43 (C12orf43), mRNA. OASL 2'-5'-oligoadenylate synthetase-like (OASL), transcript variant 3, mRNA. DQ570466 piRNA piR-30577, complete sequence. P2RX4 purinergic receptor P2X, ligand-gated ion channel, 4 (P2RX4), transcript variant 6, mRNA. CAMKK2 calcium/calmodulin-dependent protein kinase kinase 2, beta (CAMKK2), transcript variant 9, mRNA. IBD: shared region on chromosome 12 (119,306,069-128,579,558) 2 ANAPC5 anaphase promoting complex subunit 5 (ANAPC5), transcript variant 2, mRNA. RNF34 ring finger protein 34, E3 ubiquitin protein ligase (RNF34), transcript variant 3, mRNA. BC029038 cDNA clone IMAGE:5188873, partial cds. KDM2B lysine (K)-specific demethylase 2B (KDM2B), transcript variant 2, mRNA. ORAI1 ORAI calcium release-activated calcium modulator 1 (ORAI1), mRNA. MORN3 MORN repeat containing 3 (MORN3), mRNA. TMEM120B transmembrane protein 120B (TMEM120B), mRNA. AK123181 cDNA FLJ41186 fis, clone BRACE2044105. RHOF ras homolog family member F (in filopodia) (RHOF), mRNA. AK095700 cDNA FLJ37163 fis, clone BRACE2026971. SETD1B SET domain containing 1B (SETD1B), mRNA. HPD 4-hydroxyphenylpyruvate dioxygenase (HPD), transcript variant 2, mRNA. PSMD9 proteasome (prosome, macropain) 26S subunit, non-ATPase, 9 (PSMD9), transcript variant 2, mRNA. WDR66 WD repeat domain 66 (WDR66), transcript variant 2, mRNA. JB023063 Sequence 754 from Patent WO2010139812. BCL7A B-cell CLL/lymphoma 7A (BCL7A), transcript variant 2, mRNA. MLXIP MLX interacting protein (MLXIP), mRNA. LRRC43 leucine rich repeat containing 43 (LRRC43), transcript variant 2, mRNA. IL31 interleukin 31 (IL31), mRNA. B3GNT4 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4 (B3GNT4), mRNA. DIABLO diablo, IAP-binding mitochondrial protein (DIABLO), nuclear gene encoding mitochondrial protein, transcript var VPS33A vacuolar protein sorting 33 homolog A (S. cerevisiae) (VPS33A), mRNA. CLIP1 CAP-GLY domain containing linker protein 1 (CLIP1), transcript variant 3, mRNA. TRNA_Asp transfer RNA Asp (anticodon GTC) ZCCHC8 zinc finger, CCHC domain containing 8 (ZCCHC8), mRNA. SNORA9 Rfam model RF00411 hit found at contig region AC127002.3/73086-72958 RSRC2 arginine/serine-rich coiled-coil 2 (RSRC2), transcript variant 1, mRNA. KNTC1 kinetochore associated 1 (KNTC1), mRNA. HCAR1 hydroxycarboxylic acid receptor 1 (HCAR1), mRNA. HCAR2 hydroxycarboxylic acid receptor 2 (HCAR2), mRNA. HCAR3 hydroxycarboxylic acid receptor 3 (HCAR3), mRNA. DENR density-regulated protein (DENR), mRNA. CCDC62 coiled-coil domain containing 62 (CCDC62), transcript variant 2, mRNA. HIP1R huntingtin interacting protein 1 related (HIP1R), mRNA. 12 VPS37B vacuolar protein sorting 37 homolog B (S. cerevisiae) (VPS37B), mRNA. ABCB9 ATP-binding cassette, sub-family B (MDR/TAP), member 9 (ABCB9), transcript variant 6, mRNA. OGFOD2 2-oxoglutarate and iron-dependent oxygenase domain containing 2 (OGFOD2), mRNA. ARL6IP4 ADP-ribosylation-like factor 6 interacting protein 4 (ARL6IP4), transcript variant 3, mRNA. PITPNM2 phosphatidylinositol transfer protein, membrane-associated 2 (PITPNM2), mRNA. IBD: shared region on chromosome 12 (119,306,069-128,579,558) 3 MIR4304 microRNA 4304 (MIR4304), microRNA. MPHOSPH9 M-phase phosphoprotein 9 (MPHOSPH9), transcript variant 1, mRNA. C12orf65 chromosome 12 open reading frame 65 (C12orf65), transcript variant 3, mRNA. CDK2AP1 cyclin-dependent kinase 2 associated protein 1 (CDK2AP1), transcript variant 3, mRNA. SBNO1 strawberry notch homolog 1 (Drosophila) (SBNO1), transcript variant 2, mRNA. SETD8 SET domain containing (lysine methyltransferase) 8 (SETD8), mRNA. RILPL2 Rab interacting lysosomal protein-like 2 (RILPL2), mRNA. SNRNP35 small nuclear ribonucleoprotein 35kDa (U11/U12) (SNRNP35), transcript variant 3, mRNA. RILPL1 Rab interacting lysosomal protein-like 1 (RILPL1), mRNA. MIR3908 microRNA 3908 (MIR3908), microRNA. TMED2 transmembrane emp24 domain trafficking protein 2 (TMED2), mRNA. DDX55 DEAD (Asp-Glu-Ala-Asp) box polypeptide 55 (DDX55), mRNA. EIF2B1 eukaryotic translation initiation factor 2B, subunit 1 alpha, 26kDa (EIF2B1), mRNA. GTF2H3 general transcription factor IIH, polypeptide 3, 34kDa (GTF2H3), transcript variant 4, mRNA. TCTN2 tectonic family member 2 (TCTN2), transcript variant 2, mRNA. ATP6V0A2 ATPase, H+ transporting, lysosomal V0 subunit a2 (ATP6V0A2), mRNA. DNAH10 dynein, axonemal, heavy chain 10 (DNAH10), mRNA. CCDC92 coiled-coil domain containing 92 (CCDC92), mRNA. ZNF664 zinc finger protein 664 (ZNF664), transcript variant 2, mRNA. FAM101A family with sequence similarity 101, member A (FAM101A), mRNA. NCOR2 nuclear receptor corepressor 2 (NCOR2), transcript variant 3, mRNA. BC017209 cDNA clone IMAGE:3504047. SCARB1 scavenger receptor class B, member 1 (SCARB1), transcript variant 2, mRNA. JB074994 Sequence 64 from Patent WO2010139812. UBC ubiquitin C (UBC), mRNA. MIR5188 microRNA 5188 (MIR5188), microRNA. TRNA_Ala transfer RNA Ala (anticodon TGC) TRNA_Asp transfer RNA Asp (anticodon GTC) TRNA_Phe transfer RNA Phe (anticodon GAA) AX721264 Sequence 207 from Patent WO0220754. TRNA_Asp transfer RNA Asp (anticodon GTC) TRNA_Ala transfer RNA Ala (anticodon TGC) DHX37 DEAH (Asp-Glu-Ala-His) box polypeptide 37 (DHX37), mRNA. BRI3BP BRI3 binding protein (BRI3BP), mRNA. 12 DL490908 cDNA: FLJ22113 fis, clone HEP18418. AACS acetoacetyl-CoA synthetase (AACS), mRNA. TMEM132B transmembrane protein 132B (TMEM132B), mRNA. AK094786 cDNA FLJ34193 fis, clone FCBBF3018173. BC032874 cDNA clone IMAGE:4829480. Inserm UMR_S1087 / Richard Redon

Inserm U1087 Teams 1 & 4 Hôpital Laennec Marie Marrec Matthieu Pichelin CRB Plateform GenoBiRD