Caution: These are Prototype Reports for Evaluation Purposes Only!

MGD Full QTL Report

J# 20991 Kono et al., 1994

Bibliographic information for J20991

Phenotype Information

Progeny Population Information

Methods

QTL Data

Candidate Genes

General Comments

Phenotype Information for J20991

Phenotype Class: Resistance/Susceptibility
Phenotype Mode: Spontaneous
- Induced by: NULL
Phenotype Name: Susceptibility to Lupus
- Phenotype Trait 1: Mortality
- Phenotype Assessment: qualitative
- Phenotype Trait 2: Glomerulonephritis (GN)
- Phenotype Assessment: semi-quantitative
- Phenotype Trait 1: Anti-chromatin antibody production
- Phenotype Assessment: qualitative
- Phenotype Trait 1: Splenomegaly
- Phenotype Assessment: quantitative
Alternative Keywords: autoimmune disease, systemic lupus erythematosus, SLE
Strain/Progenitor Information:
- Strain 1: NAB/BlScr
- Strain 1 Comment: NULL
- Strain 2: NZW/LacScr
- Strain 2 Comment: NULL
Phenotype Comments: NULL

Progeny Population for J20991

Progeny Generation Used for QTL Experiment: F2
Progeny Population Name: BWF2
# Animals Evaluated: NULL
Female Parent:(NZB X NZW)F1
Male Parent: (NZB X NZW)F1
Cross Type: intercross
Another cross for this progeny population?: No
Comments:
- 1) Only female mice evaluated for traits
- 2) F1 progeny also refered to as BWF1

Methods for J20991

Chromosomes Included in Marker Map Construction: All
Marker Map Methods:
- PCR-micrsatellites
Number of Markers in Analysis: 91
Intermarker Distance:longest interval from gene to marker ranges from 14 to 30 cM
Comments on Marker Map:
- Autosomal genome coverage estimated at 97%
QTL Detection Method: Chi square
- Other QTL Detection Method: NULL
Significance Threshold for QTL Detection: P < 0.001
- Significance Threshold Comment:NULL
QTL Estimation Method: interval mapping
Comments on QTL Estimation Model Used: NULL
QTL Mapping Software: MapMaker

QTL Information for J20991

Phenotype Trait: Mortality

QTL Symbol: Lbw1

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw1 tnfa 9.5 < 0.01 17
QTL Estimation:
- Chromosome: 17
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments: NULL

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw1	tnfa	9.5	< 0.01	17

Phenotype Trait: Antichromatin antibody production

QTL Symbol: Lbw1

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw1 tnfa 17.3 < 0.001 17
QTL Estimation:
- Chromosome: 17
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments: NULL

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw1	tnfa	17.3	< 0.001	17

Phenotype Trait:Glomerulonephritis (GN)

QTL Symbol: Lbw1

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw1 Hsp68 17.4 < 0.001 17
QTL Estimation:
- Chromosome: 17
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments: NULL

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw1	Hsp68	17.4	< 0.001	17

Phenotype Trait: Mortality

QTL Symbol: Lbw2

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw2 D4Nds2 23.5 < 0.001 4
QTL Estimation:
- Chromosome: 4
- Location: 9 cM span between markers D4Mit16 and D4Mit28
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments: NULL
- 1) Lbw2 appears to contribute a dominant NZB autoimmune susceptibility allele
- 2) Lbw2 is strongly associated with early mortality
- 3) Fine mapping of Lbw2 was accomplished by analyzing only phenotype-positive early death individuals and was based on 10 informative crossover events.

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw2	D4Nds2	23.5	< 0.001	4

Phenotype Trait:Glomerulonephritis (GN)

QTL Symbol: Lbw2

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw2 D4Nds2 13.8 < 0.001 4
QTL Estimation:
- Chromosome: 4
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments: NULL

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw2	D4Nds2	13.8	< 0.001	4

Phenotype Trait:Glomerulonephritis (GN)

QTL Symbol: Lbw3

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw3 D5Mit101 14.1 < 0.001 5
QTL Estimation:
- Chromosome: 5
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments:
- 1) Lbw3 appear to contribute a recessive NZB autoimmune susceptibility allele

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw3	D5Mit101	14.1	< 0.001	5

Phenotype Trait:Glomerulonephritis (GN)

QTL Symbol: Lbw4

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw4 D6Mit25 10.0 < 0.01 6
QTL Estimation:
- Chromosome: 5
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments:NULL

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw4	D6Mit25	10.0	< 0.01	6

Phenotype Trait: Mortality

QTL Symbol: Lbw5

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw5 Ngfg 10.6 < 0.01 7
QTL Estimation:
- Chromosome: 5
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments:
- 1) Lbw5 appears to contribute a dominant NZW susceptibility allele

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw5	Ngfg	10.6	< 0.01	7

Phenotype Trait: Mortality

QTL Symbol: Lbw6

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw6 D18Mit8 10.9 < 0.005 18
QTL Estimation:
- Chromosome: 18
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments:
- 1) Lbw6 appears to contribute a recessive NZW autoimmune susceptibility allele

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw6	D18Mit8	10.9	< 0.005	18

Phenotype Trait:Glomerulonephritis (GN)

QTL Symbol: Lbw6

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw6 D18Mit8 15.1 < 0.001 18
QTL Estimation:
- Chromosome: 18
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments:NULL

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw6	D18Mit8	15.1	< 0.001	18

Phenotype Trait: Antichromatin antibody production

QTL Symbol: Lbw7

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw7 D1Mit36 12.0 < 0.005 1
QTL Estimation:
- Chromosome: 1
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments:
- 1) Lbw7 appears to contribute to NZB susceptibility

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw7	D1Mit36	12.0	< 0.005	1

Phenotype Trait: Antichromatin antibody production

QTL Symbol: Lbw8

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Lbw7 Il4 10.7 < 0.005 11
QTL Estimation:
- Chromosome: 11
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments:
- 1) Lbw8 appears to contribute to NZB susceptibility

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Lbw7	Il4	10.7	< 0.005	11

Phenotype Trait:Splenomegaly

QTL Symbol: Sbw1

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Sbw1 D1Nds1 13.09 < 0.005 1
QTL Estimation:
- Chromosome: 1
- Location: NULL
- % Phenotypic Variation Accounted For: NULL
- Confidence Interval for QTL Estimation: NULL
Comments:
- 1) Splenomegaly appears to exhibit incomplete dominant inheritance

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Sbw1	D1Nds1	13.09	< 0.005	1

Phenotype Trait:Splenomegaly

QTL Symbol: Sbw2

QTL Detection Method: Chi square
Table of Linked Markers:

QTL Symbol Linked Marker Symbol Association Score P Value Chromosome

Sbw2 D4Mit9 25.4 << 0.005 4
QTL Estimation:
- Chromosome: 4
- Location: NULL
- % Phenotypic Variation Accounted For: 7 cM region between D4Mit16 and D4Nds2
- Confidence Interval for QTL Estimation: NULL
Comments:
- 1) Sbw2 has an additive pattern of inheritance
- 2) Sbw2 and Lbw2 map to the same region; may be a single gene with pleiotropic effects
- 3) Fine mapping of Sbw2 included all mice with splenomegaly with five informative crossover events

QTL Symbol	Linked Marker Symbol	Association Score	P Value	Chromosome
Sbw2	D4Mit9	25.4	<< 0.005	4

Candidate Genes for QTLs Reported in J20991

QTL Symbol(s)	Candidate Gene Symbol	Chromosome	Gene Name
Lbw7, Sbw1	Cd28	1	CD28 antigen
Lbw7, Sbw1	Ctla4	1	cytotoxic T lymphocyte-associated protein 4
Lbw7, Sbw1	Bcl2	1	B-cell leukemia/lymphoma 2
Lbw7, Sbw1	Il10	1	interleukin 10
Lbw2	Bmfr1	4	B cell maturation factor responsiveness 1
Lbw4	Il5r	4	interleukin 5 receptor
Lbw4	Tnfr1	1	tumor necrosis factor 1
Lbw8	Il4	11	interleukin 4
Lbw8	Il5	11	interleukin 5
Lbw8	Irf1	11	interferon regulatory factor 1
Lbw8	Trp53	11	transformation-related protein 53

Comments:NULL

Overall Comments for J20991:

1) Results suggest that a recessive NZB Sbw1 allel and a dominant NZB Sbw2 allele contribute to splenomegaly.

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