Related Experiment Video
Updated: Aug 5, 2026
05:30
Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
XXYLT1 and Mendelian Retinal Dystrophy
Minna Kraatari-Tiri1,2, Hina Ishtiaq1,2, Jaakko Tyrmi3,4
1Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland.
JAMA Ophthalmology
|July 30, 2026
Summary
Genome-wide association studies (GWAS) identified a link between the XXYLT1 gene and inherited retinal disease (IRD). This highlights GWAS as a tool for discovering rare disease genes and suggests XXYLT1 for IRD gene panels.
Area of Science:
- Genetics
- Ophthalmology
- Genomic Medicine
Background:
- Unexplained heritability persists for pathogenic inherited retinal disease (IRD) variants.
- Genome-wide association studies (GWAS) offer a method to identify genes implicated in rare diseases.
Purpose of the Study:
- To utilize GWAS for discovering genes associated with inherited retinal disease (IRD).
Main Methods:
- GWAS analysis combined with replication in two independent IRD cohorts.
- FinnGen, 100,000 Genomes Project, and NHS Genomic Medicine Service data were used.
- IRD cases were identified using ICD-9/10 criteria, with validation in clinical cohorts.
Main Results:
- GWAS identified 13 significant recessive loci, including novel associations near XXYLT1, ANKRD10, DYM, and CBLN4.
- A founder variant in XXYLT1 (c.505-1G>C) was identified in multiple families with macular dystrophy phenotypes.
- Functional studies confirmed a loss-of-function effect for the XXYLT1 variant, with replication in UK patients.
Conclusions:
- GWAS in founder populations can discover rare Mendelian disease genes.
- An association between XXYLT1 and IRD was identified.
- XXYLT1 should be considered for inclusion in clinical IRD gene panels.
Related Concept Videos
01:43Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
01:11Genetic Lingo
Overview
01:35Pedigree Analysis
Overview
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...