# GENETIC LINKAGE ANALYSIS OF INHERITED OSTEOARTHRITIS

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1988 · $150,129

## Abstract

Among the many disorders resulting in osteoarthritis, there are
several forms that are clearly genetic in origin.  These diseases
are inherited as dominant traits in a Mendelian pattern, and there
is no evidence that any environmental factor plays a major role in
etiology.  The most common of the inherited OA disorders is
primary generalized osteoarthritis (PGOA), characterized by
early-onset degeneration of multiple joints, particularly the hips
and knees, and the appearance of Heberden's nodes in the distal
phalangeal joints.  The second type of inherited OA is
chondrocalcinosis (CC) resulting from deposits of calcium
phosphate dihydrate in the joints.  The third familial OA is
Wagner-Stickler syndrome, or arthro-ophthalmopathy (AO), the
symptoms of which include retinopathy in addition to the
degenerative joint disease.  The objective of this research is to
identify the genes at fault in these disorders through genetic
linkage analysis.  Restriction fragment length polymorphisms
(RFLPs) will be used to test genes expressed in cartilage and
other candidate chromosomal loci for genetic linkage to inherited
OA.  The results will conclusively rule out some genes as the site
of the primary defect and strongly implicate others that show
close genetic linkage.  These studies will begin with genes for
major cartilage proteins (such as type II and type VI procollagen).
Forms of inherited OA not linked to any of the candidate
cartilage genes will be mapped by linkage to one or more of the
many highly polymorphic anonymous RFLPs now available for
human chromosome mapping.  Genetic mapping of OA in various
families will establish the extent of genetic heterogeneity of
these diseases, i.e. whether different genes are at fault in
different families.  The ultimate objective in identifying the
genes responsible for inherited forms of OA is to understand the
molecular basis of these diseases, so that more effective
prevention and treatment might be developed.  The gene products
and the pathways leading to joint degeneration in familial OA
would also become rational starting points for studying the
molecular basis of other forms of OA.

## Key facts

- **NIH application ID:** 3159614
- **Project number:** 1R01AR039530-01
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** ROBERT G KNOWLTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $150,129
- **Award type:** 1
- **Project period:** 1988-07-01 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159614

## Citation

> US National Institutes of Health, RePORTER application 3159614, GENETIC LINKAGE ANALYSIS OF INHERITED OSTEOARTHRITIS (1R01AR039530-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159614. Licensed CC0.

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