Practical summary for breeders
The BR1 test answers one specific question: does this horse carry the MBTPS2 c.1437+4T>C variant? If yes, the brindle pattern is heritable through X-linked transmission. If no, the pattern is likely not heritable. The test does not diagnose chimerism, mosaicism, or IP.
A summary of the breeding implications:
| Parent genotype | Offspring expectation |
|---|---|
| N/BR1 mare x N stallion | ~50% daughters N/BR1 (brindle coat); ~50% daughters N/N; ~50% sons BR1 hemizygous (sparse mane/tail, no stripe); ~50% sons N |
| N/N mare x BR1 stallion | All daughters N/BR1 (brindle coat expected); all sons N |
| N/N mare x N stallion | No BR1 offspring regardless of coat appearance of either parent |
The test is available from the UC Davis Veterinary Genetics Laboratory. Hair samples (pulled root-on, not cut) are the standard submission for equine coat-color genotyping.
Related reading
- Brindle Horses: Mechanisms, Genetics, and Patterns: the full framework: chimerism, mosaicism, BR1, IP
- The Genetics Behind Brindle Horses: the 2016 Murgiano study in detail: the variant, the splicing defect, the family
- Incontinentia Pigmenti in Horses: the IKBKG variant: when brindle stripes signal disease
- Blaschko’s Lines in Horses: why brindle stripes follow the body the way they do
The MBTPS2 gene: what it does
The MBTPS2 gene encodes Site-2 protease (S2P), a zinc metalloprotease embedded in the endoplasmic reticulum membrane. S2P is responsible for cleaving membrane-anchored transcription factor precursors, most importantly SREBP (sterol regulatory element-binding protein) and ATF6 (activating transcription factor 6), releasing their active forms into the nucleus where they regulate lipid metabolism and the unfolded protein response, respectively. [Murgiano et al. 2016]
Mutations in the human MBTPS2 orthologue cause three distinct genodermatoses: ichthyosis follicularis with atrichia and photophobia (IFAP syndrome), MEDNIK syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma), and keratosis follicularis spinulosa decalvans (KFSD). All three involve skin and hair pathology in humans. The equine BR1 variant does not replicate these human conditions; the equine MBTPS2 mutation produces only the coat and hair-texture change with no systemic pathology reported. The study authors noted this discrepancy and attributed it to the partial rather than complete splicing disruption: approximately 80% of transcripts in BR1-affected horses retain correct splicing, which may be sufficient for normal function in other tissues. [Murgiano et al. 2016]
Practical summary for breeders
The BR1 test answers one specific question: does this horse carry the MBTPS2 c.1437+4T>C variant? If yes, the brindle pattern is heritable through X-linked transmission. If no, the pattern is likely not heritable. The test does not diagnose chimerism, mosaicism, or IP.
A summary of the breeding implications:
| Parent genotype | Offspring expectation |
|---|---|
| N/BR1 mare x N stallion | ~50% daughters N/BR1 (brindle coat); ~50% daughters N/N; ~50% sons BR1 hemizygous (sparse mane/tail, no stripe); ~50% sons N |
| N/N mare x BR1 stallion | All daughters N/BR1 (brindle coat expected); all sons N |
| N/N mare x N stallion | No BR1 offspring regardless of coat appearance of either parent |
The test is available from the UC Davis Veterinary Genetics Laboratory. Hair samples (pulled root-on, not cut) are the standard submission for equine coat-color genotyping.
Related reading
- Brindle Horses: Mechanisms, Genetics, and Patterns: the full framework: chimerism, mosaicism, BR1, IP
- The Genetics Behind Brindle Horses: the 2016 Murgiano study in detail: the variant, the splicing defect, the family
- Incontinentia Pigmenti in Horses: the IKBKG variant: when brindle stripes signal disease
- Blaschko’s Lines in Horses: why brindle stripes follow the body the way they do
What the test does not detect
A negative BR1 result (N/N in mares, N in stallions) means the horse does not carry the specific MBTPS2 variant. It does not mean the horse cannot produce brindle offspring, and it does not mean a visibly brindle horse’s pattern has any other specific cause.
Three points matter here:
- Chimerism and somatic mosaicism are not heritable and are not detected by any routine genetic test. These mechanisms produce brindle-like coats in individual horses without any transmission of the pattern through breeding. A brindle horse that tests BR1-negative likely has chimerism or somatic mosaicism as the cause of the coat pattern. [Chimerism in Horses; Somatic Mosaicism in Horses]
- Incontinentia pigmenti (IP) is not detected by the BR1 test. IP is caused by a variant in the IKBKG gene (c.184C>T, OMIA:001899-9796), not MBTPS2. A mare with brindle-like striping and systemic findings (dental, hoof, skin lesion progression) who tests BR1-negative warrants evaluation for the IKBKG variant separately. [Incontinentia Pigmenti in Horses]
- The study was conducted in Quarter Horses. The BR1 variant was confirmed in a specific Quarter Horse family. Whether the same variant occurs in other breeds has not been systematically established. A brindle horse of a breed not represented in the Murgiano et al. study who tests positive has the variant; whether the variant behaves identically in a different genetic background has not been studied in the peer-reviewed literature.
The MBTPS2 gene: what it does
The MBTPS2 gene encodes Site-2 protease (S2P), a zinc metalloprotease embedded in the endoplasmic reticulum membrane. S2P is responsible for cleaving membrane-anchored transcription factor precursors, most importantly SREBP (sterol regulatory element-binding protein) and ATF6 (activating transcription factor 6), releasing their active forms into the nucleus where they regulate lipid metabolism and the unfolded protein response, respectively. [Murgiano et al. 2016]
Mutations in the human MBTPS2 orthologue cause three distinct genodermatoses: ichthyosis follicularis with atrichia and photophobia (IFAP syndrome), MEDNIK syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma), and keratosis follicularis spinulosa decalvans (KFSD). All three involve skin and hair pathology in humans. The equine BR1 variant does not replicate these human conditions; the equine MBTPS2 mutation produces only the coat and hair-texture change with no systemic pathology reported. The study authors noted this discrepancy and attributed it to the partial rather than complete splicing disruption: approximately 80% of transcripts in BR1-affected horses retain correct splicing, which may be sufficient for normal function in other tissues. [Murgiano et al. 2016]
Practical summary for breeders
The BR1 test answers one specific question: does this horse carry the MBTPS2 c.1437+4T>C variant? If yes, the brindle pattern is heritable through X-linked transmission. If no, the pattern is likely not heritable. The test does not diagnose chimerism, mosaicism, or IP.
A summary of the breeding implications:
| Parent genotype | Offspring expectation |
|---|---|
| N/BR1 mare x N stallion | ~50% daughters N/BR1 (brindle coat); ~50% daughters N/N; ~50% sons BR1 hemizygous (sparse mane/tail, no stripe); ~50% sons N |
| N/N mare x BR1 stallion | All daughters N/BR1 (brindle coat expected); all sons N |
| N/N mare x N stallion | No BR1 offspring regardless of coat appearance of either parent |
The test is available from the UC Davis Veterinary Genetics Laboratory. Hair samples (pulled root-on, not cut) are the standard submission for equine coat-color genotyping.
Related reading
- Brindle Horses: Mechanisms, Genetics, and Patterns: the full framework: chimerism, mosaicism, BR1, IP
- The Genetics Behind Brindle Horses: the 2016 Murgiano study in detail: the variant, the splicing defect, the family
- Incontinentia Pigmenti in Horses: the IKBKG variant: when brindle stripes signal disease
- Blaschko’s Lines in Horses: why brindle stripes follow the body the way they do
Reading the result: stallions
Stallions have one X chromosome and one Y chromosome. The result for a stallion is reported as N (hemizygous normal) or BR1 (hemizygous for the variant).
- N: No BR1 variant. The stallion will not pass BR1 to any offspring.
- BR1: One copy of the variant (hemizygous, carried on the single X). These stallions do not show the brindle coat pattern. Instead, the 2016 study reported that hemizygous BR1 males express sparse mane and tail with no visible stripe pattern on the body. The variant is present and will be passed to all of the stallion’s daughters, none of his sons. All daughters from a BR1 stallion will be N/BR1 (heterozygous, and therefore expected to show the brindle coat pattern if their dam contributes a normal X allele). [Murgiano et al. 2016]
What the test does not detect
A negative BR1 result (N/N in mares, N in stallions) means the horse does not carry the specific MBTPS2 variant. It does not mean the horse cannot produce brindle offspring, and it does not mean a visibly brindle horse’s pattern has any other specific cause.
Three points matter here:
- Chimerism and somatic mosaicism are not heritable and are not detected by any routine genetic test. These mechanisms produce brindle-like coats in individual horses without any transmission of the pattern through breeding. A brindle horse that tests BR1-negative likely has chimerism or somatic mosaicism as the cause of the coat pattern. [Chimerism in Horses; Somatic Mosaicism in Horses]
- Incontinentia pigmenti (IP) is not detected by the BR1 test. IP is caused by a variant in the IKBKG gene (c.184C>T, OMIA:001899-9796), not MBTPS2. A mare with brindle-like striping and systemic findings (dental, hoof, skin lesion progression) who tests BR1-negative warrants evaluation for the IKBKG variant separately. [Incontinentia Pigmenti in Horses]
- The study was conducted in Quarter Horses. The BR1 variant was confirmed in a specific Quarter Horse family. Whether the same variant occurs in other breeds has not been systematically established. A brindle horse of a breed not represented in the Murgiano et al. study who tests positive has the variant; whether the variant behaves identically in a different genetic background has not been studied in the peer-reviewed literature.
The MBTPS2 gene: what it does
The MBTPS2 gene encodes Site-2 protease (S2P), a zinc metalloprotease embedded in the endoplasmic reticulum membrane. S2P is responsible for cleaving membrane-anchored transcription factor precursors, most importantly SREBP (sterol regulatory element-binding protein) and ATF6 (activating transcription factor 6), releasing their active forms into the nucleus where they regulate lipid metabolism and the unfolded protein response, respectively. [Murgiano et al. 2016]
Mutations in the human MBTPS2 orthologue cause three distinct genodermatoses: ichthyosis follicularis with atrichia and photophobia (IFAP syndrome), MEDNIK syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma), and keratosis follicularis spinulosa decalvans (KFSD). All three involve skin and hair pathology in humans. The equine BR1 variant does not replicate these human conditions; the equine MBTPS2 mutation produces only the coat and hair-texture change with no systemic pathology reported. The study authors noted this discrepancy and attributed it to the partial rather than complete splicing disruption: approximately 80% of transcripts in BR1-affected horses retain correct splicing, which may be sufficient for normal function in other tissues. [Murgiano et al. 2016]
Practical summary for breeders
The BR1 test answers one specific question: does this horse carry the MBTPS2 c.1437+4T>C variant? If yes, the brindle pattern is heritable through X-linked transmission. If no, the pattern is likely not heritable. The test does not diagnose chimerism, mosaicism, or IP.
A summary of the breeding implications:
| Parent genotype | Offspring expectation |
|---|---|
| N/BR1 mare x N stallion | ~50% daughters N/BR1 (brindle coat); ~50% daughters N/N; ~50% sons BR1 hemizygous (sparse mane/tail, no stripe); ~50% sons N |
| N/N mare x BR1 stallion | All daughters N/BR1 (brindle coat expected); all sons N |
| N/N mare x N stallion | No BR1 offspring regardless of coat appearance of either parent |
The test is available from the UC Davis Veterinary Genetics Laboratory. Hair samples (pulled root-on, not cut) are the standard submission for equine coat-color genotyping.
Related reading
- Brindle Horses: Mechanisms, Genetics, and Patterns: the full framework: chimerism, mosaicism, BR1, IP
- The Genetics Behind Brindle Horses: the 2016 Murgiano study in detail: the variant, the splicing defect, the family
- Incontinentia Pigmenti in Horses: the IKBKG variant: when brindle stripes signal disease
- Blaschko’s Lines in Horses: why brindle stripes follow the body the way they do
Reading the result: mares
Mares have two X chromosomes. The result for a mare is reported as N/N, N/BR1, or BR1/BR1.
- N/N: No copies of the BR1 variant. The mare does not carry heritable brindle at this locus. If she has a brindle coat, the pattern is caused by chimerism, somatic mosaicism, incontinentia pigmenti, or another uncharacterized mechanism, not the MBTPS2 BR1 variant.
- N/BR1: One copy of the BR1 variant. This is the genotype that produces the characteristic visible brindle coat with altered hair texture in mares. Inheritance is X-linked semidominant: the variant is expressed in the heterozygous state. Approximately half of this mare’s daughters will inherit the BR1 allele and show the pattern; approximately half of her sons will inherit the BR1 allele and show sparse mane and tail but not the visible coat pattern. [Murgiano et al. 2016]
- BR1/BR1: Two copies. Homozygous mares carry the variant on both X chromosomes. Whether they are phenotypically distinct from N/BR1 mares has not been reported in the literature; the 2016 study did not document homozygous individuals. All of this mare’s daughters will inherit one BR1 allele; all sons will inherit one BR1 allele.
Reading the result: stallions
Stallions have one X chromosome and one Y chromosome. The result for a stallion is reported as N (hemizygous normal) or BR1 (hemizygous for the variant).
- N: No BR1 variant. The stallion will not pass BR1 to any offspring.
- BR1: One copy of the variant (hemizygous, carried on the single X). These stallions do not show the brindle coat pattern. Instead, the 2016 study reported that hemizygous BR1 males express sparse mane and tail with no visible stripe pattern on the body. The variant is present and will be passed to all of the stallion’s daughters, none of his sons. All daughters from a BR1 stallion will be N/BR1 (heterozygous, and therefore expected to show the brindle coat pattern if their dam contributes a normal X allele). [Murgiano et al. 2016]
What the test does not detect
A negative BR1 result (N/N in mares, N in stallions) means the horse does not carry the specific MBTPS2 variant. It does not mean the horse cannot produce brindle offspring, and it does not mean a visibly brindle horse’s pattern has any other specific cause.
Three points matter here:
- Chimerism and somatic mosaicism are not heritable and are not detected by any routine genetic test. These mechanisms produce brindle-like coats in individual horses without any transmission of the pattern through breeding. A brindle horse that tests BR1-negative likely has chimerism or somatic mosaicism as the cause of the coat pattern. [Chimerism in Horses; Somatic Mosaicism in Horses]
- Incontinentia pigmenti (IP) is not detected by the BR1 test. IP is caused by a variant in the IKBKG gene (c.184C>T, OMIA:001899-9796), not MBTPS2. A mare with brindle-like striping and systemic findings (dental, hoof, skin lesion progression) who tests BR1-negative warrants evaluation for the IKBKG variant separately. [Incontinentia Pigmenti in Horses]
- The study was conducted in Quarter Horses. The BR1 variant was confirmed in a specific Quarter Horse family. Whether the same variant occurs in other breeds has not been systematically established. A brindle horse of a breed not represented in the Murgiano et al. study who tests positive has the variant; whether the variant behaves identically in a different genetic background has not been studied in the peer-reviewed literature.
The MBTPS2 gene: what it does
The MBTPS2 gene encodes Site-2 protease (S2P), a zinc metalloprotease embedded in the endoplasmic reticulum membrane. S2P is responsible for cleaving membrane-anchored transcription factor precursors, most importantly SREBP (sterol regulatory element-binding protein) and ATF6 (activating transcription factor 6), releasing their active forms into the nucleus where they regulate lipid metabolism and the unfolded protein response, respectively. [Murgiano et al. 2016]
Mutations in the human MBTPS2 orthologue cause three distinct genodermatoses: ichthyosis follicularis with atrichia and photophobia (IFAP syndrome), MEDNIK syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma), and keratosis follicularis spinulosa decalvans (KFSD). All three involve skin and hair pathology in humans. The equine BR1 variant does not replicate these human conditions; the equine MBTPS2 mutation produces only the coat and hair-texture change with no systemic pathology reported. The study authors noted this discrepancy and attributed it to the partial rather than complete splicing disruption: approximately 80% of transcripts in BR1-affected horses retain correct splicing, which may be sufficient for normal function in other tissues. [Murgiano et al. 2016]
Practical summary for breeders
The BR1 test answers one specific question: does this horse carry the MBTPS2 c.1437+4T>C variant? If yes, the brindle pattern is heritable through X-linked transmission. If no, the pattern is likely not heritable. The test does not diagnose chimerism, mosaicism, or IP.
A summary of the breeding implications:
| Parent genotype | Offspring expectation |
|---|---|
| N/BR1 mare x N stallion | ~50% daughters N/BR1 (brindle coat); ~50% daughters N/N; ~50% sons BR1 hemizygous (sparse mane/tail, no stripe); ~50% sons N |
| N/N mare x BR1 stallion | All daughters N/BR1 (brindle coat expected); all sons N |
| N/N mare x N stallion | No BR1 offspring regardless of coat appearance of either parent |
The test is available from the UC Davis Veterinary Genetics Laboratory. Hair samples (pulled root-on, not cut) are the standard submission for equine coat-color genotyping.
Related reading
- Brindle Horses: Mechanisms, Genetics, and Patterns: the full framework: chimerism, mosaicism, BR1, IP
- The Genetics Behind Brindle Horses: the 2016 Murgiano study in detail: the variant, the splicing defect, the family
- Incontinentia Pigmenti in Horses: the IKBKG variant: when brindle stripes signal disease
- Blaschko’s Lines in Horses: why brindle stripes follow the body the way they do
What the test is
The BR1 test from UC Davis VGL detects the presence or absence of the MBTPS2 c.1437+4T>C variant (genomic position NC_009175.3:g.17286855T>C on the X chromosome, EquCab3.0 assembly). This is the specific variant identified by Murgiano, Waluk, Towers, and colleagues in a family of American Quarter Horses and confirmed to co-segregate perfectly with the brindle phenotype across 39 family members, absent from 457 control horses spanning 17 breeds. [Murgiano et al. 2016] The OMIA record is OMIA:002021-9796.
The test uses a hair or blood sample and returns one of three genotype calls, using the notation N (normal) and BR1 (the brindle variant allele).
Reading the result: mares
Mares have two X chromosomes. The result for a mare is reported as N/N, N/BR1, or BR1/BR1.
- N/N: No copies of the BR1 variant. The mare does not carry heritable brindle at this locus. If she has a brindle coat, the pattern is caused by chimerism, somatic mosaicism, incontinentia pigmenti, or another uncharacterized mechanism, not the MBTPS2 BR1 variant.
- N/BR1: One copy of the BR1 variant. This is the genotype that produces the characteristic visible brindle coat with altered hair texture in mares. Inheritance is X-linked semidominant: the variant is expressed in the heterozygous state. Approximately half of this mare’s daughters will inherit the BR1 allele and show the pattern; approximately half of her sons will inherit the BR1 allele and show sparse mane and tail but not the visible coat pattern. [Murgiano et al. 2016]
- BR1/BR1: Two copies. Homozygous mares carry the variant on both X chromosomes. Whether they are phenotypically distinct from N/BR1 mares has not been reported in the literature; the 2016 study did not document homozygous individuals. All of this mare’s daughters will inherit one BR1 allele; all sons will inherit one BR1 allele.
Reading the result: stallions
Stallions have one X chromosome and one Y chromosome. The result for a stallion is reported as N (hemizygous normal) or BR1 (hemizygous for the variant).
- N: No BR1 variant. The stallion will not pass BR1 to any offspring.
- BR1: One copy of the variant (hemizygous, carried on the single X). These stallions do not show the brindle coat pattern. Instead, the 2016 study reported that hemizygous BR1 males express sparse mane and tail with no visible stripe pattern on the body. The variant is present and will be passed to all of the stallion’s daughters, none of his sons. All daughters from a BR1 stallion will be N/BR1 (heterozygous, and therefore expected to show the brindle coat pattern if their dam contributes a normal X allele). [Murgiano et al. 2016]
What the test does not detect
A negative BR1 result (N/N in mares, N in stallions) means the horse does not carry the specific MBTPS2 variant. It does not mean the horse cannot produce brindle offspring, and it does not mean a visibly brindle horse’s pattern has any other specific cause.
Three points matter here:
- Chimerism and somatic mosaicism are not heritable and are not detected by any routine genetic test. These mechanisms produce brindle-like coats in individual horses without any transmission of the pattern through breeding. A brindle horse that tests BR1-negative likely has chimerism or somatic mosaicism as the cause of the coat pattern. [Chimerism in Horses; Somatic Mosaicism in Horses]
- Incontinentia pigmenti (IP) is not detected by the BR1 test. IP is caused by a variant in the IKBKG gene (c.184C>T, OMIA:001899-9796), not MBTPS2. A mare with brindle-like striping and systemic findings (dental, hoof, skin lesion progression) who tests BR1-negative warrants evaluation for the IKBKG variant separately. [Incontinentia Pigmenti in Horses]
- The study was conducted in Quarter Horses. The BR1 variant was confirmed in a specific Quarter Horse family. Whether the same variant occurs in other breeds has not been systematically established. A brindle horse of a breed not represented in the Murgiano et al. study who tests positive has the variant; whether the variant behaves identically in a different genetic background has not been studied in the peer-reviewed literature.
The MBTPS2 gene: what it does
The MBTPS2 gene encodes Site-2 protease (S2P), a zinc metalloprotease embedded in the endoplasmic reticulum membrane. S2P is responsible for cleaving membrane-anchored transcription factor precursors, most importantly SREBP (sterol regulatory element-binding protein) and ATF6 (activating transcription factor 6), releasing their active forms into the nucleus where they regulate lipid metabolism and the unfolded protein response, respectively. [Murgiano et al. 2016]
Mutations in the human MBTPS2 orthologue cause three distinct genodermatoses: ichthyosis follicularis with atrichia and photophobia (IFAP syndrome), MEDNIK syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma), and keratosis follicularis spinulosa decalvans (KFSD). All three involve skin and hair pathology in humans. The equine BR1 variant does not replicate these human conditions; the equine MBTPS2 mutation produces only the coat and hair-texture change with no systemic pathology reported. The study authors noted this discrepancy and attributed it to the partial rather than complete splicing disruption: approximately 80% of transcripts in BR1-affected horses retain correct splicing, which may be sufficient for normal function in other tissues. [Murgiano et al. 2016]
Practical summary for breeders
The BR1 test answers one specific question: does this horse carry the MBTPS2 c.1437+4T>C variant? If yes, the brindle pattern is heritable through X-linked transmission. If no, the pattern is likely not heritable. The test does not diagnose chimerism, mosaicism, or IP.
A summary of the breeding implications:
| Parent genotype | Offspring expectation |
|---|---|
| N/BR1 mare x N stallion | ~50% daughters N/BR1 (brindle coat); ~50% daughters N/N; ~50% sons BR1 hemizygous (sparse mane/tail, no stripe); ~50% sons N |
| N/N mare x BR1 stallion | All daughters N/BR1 (brindle coat expected); all sons N |
| N/N mare x N stallion | No BR1 offspring regardless of coat appearance of either parent |
The test is available from the UC Davis Veterinary Genetics Laboratory. Hair samples (pulled root-on, not cut) are the standard submission for equine coat-color genotyping.
Related reading
- Brindle Horses: Mechanisms, Genetics, and Patterns: the full framework: chimerism, mosaicism, BR1, IP
- The Genetics Behind Brindle Horses: the 2016 Murgiano study in detail: the variant, the splicing defect, the family
- Incontinentia Pigmenti in Horses: the IKBKG variant: when brindle stripes signal disease
- Blaschko’s Lines in Horses: why brindle stripes follow the body the way they do
There is now a commercial genetic test for one form of heritable brindle in horses. The UC Davis Veterinary Genetics Laboratory (VGL) offers a test for the BR1 variant: a specific intronic mutation in the MBTPS2 gene, confirmed in a peer-reviewed study in 2016 as the cause of a heritable X-linked brindle pattern in Quarter Horses. [Murgiano et al., G3: Genes|Genomes|Genetics, 2016, doi:10.1534/g3.116.032433; UC Davis VGL]
What a positive test confirms, and what it does not confirm, are both important for anyone making breeding decisions based on a brindle coat pattern. Brindle in horses is caused by at least three distinct mechanisms, only one of which this test detects. A negative result does not mean a brindle horse is non-brindle. A positive result carries specific breeding implications that differ from all other coat-color variants in common use.
What the test is
The BR1 test from UC Davis VGL detects the presence or absence of the MBTPS2 c.1437+4T>C variant (genomic position NC_009175.3:g.17286855T>C on the X chromosome, EquCab3.0 assembly). This is the specific variant identified by Murgiano, Waluk, Towers, and colleagues in a family of American Quarter Horses and confirmed to co-segregate perfectly with the brindle phenotype across 39 family members, absent from 457 control horses spanning 17 breeds. [Murgiano et al. 2016] The OMIA record is OMIA:002021-9796.
The test uses a hair or blood sample and returns one of three genotype calls, using the notation N (normal) and BR1 (the brindle variant allele).
Reading the result: mares
Mares have two X chromosomes. The result for a mare is reported as N/N, N/BR1, or BR1/BR1.
- N/N: No copies of the BR1 variant. The mare does not carry heritable brindle at this locus. If she has a brindle coat, the pattern is caused by chimerism, somatic mosaicism, incontinentia pigmenti, or another uncharacterized mechanism, not the MBTPS2 BR1 variant.
- N/BR1: One copy of the BR1 variant. This is the genotype that produces the characteristic visible brindle coat with altered hair texture in mares. Inheritance is X-linked semidominant: the variant is expressed in the heterozygous state. Approximately half of this mare’s daughters will inherit the BR1 allele and show the pattern; approximately half of her sons will inherit the BR1 allele and show sparse mane and tail but not the visible coat pattern. [Murgiano et al. 2016]
- BR1/BR1: Two copies. Homozygous mares carry the variant on both X chromosomes. Whether they are phenotypically distinct from N/BR1 mares has not been reported in the literature; the 2016 study did not document homozygous individuals. All of this mare’s daughters will inherit one BR1 allele; all sons will inherit one BR1 allele.
Reading the result: stallions
Stallions have one X chromosome and one Y chromosome. The result for a stallion is reported as N (hemizygous normal) or BR1 (hemizygous for the variant).
- N: No BR1 variant. The stallion will not pass BR1 to any offspring.
- BR1: One copy of the variant (hemizygous, carried on the single X). These stallions do not show the brindle coat pattern. Instead, the 2016 study reported that hemizygous BR1 males express sparse mane and tail with no visible stripe pattern on the body. The variant is present and will be passed to all of the stallion’s daughters, none of his sons. All daughters from a BR1 stallion will be N/BR1 (heterozygous, and therefore expected to show the brindle coat pattern if their dam contributes a normal X allele). [Murgiano et al. 2016]
What the test does not detect
A negative BR1 result (N/N in mares, N in stallions) means the horse does not carry the specific MBTPS2 variant. It does not mean the horse cannot produce brindle offspring, and it does not mean a visibly brindle horse’s pattern has any other specific cause.
Three points matter here:
- Chimerism and somatic mosaicism are not heritable and are not detected by any routine genetic test. These mechanisms produce brindle-like coats in individual horses without any transmission of the pattern through breeding. A brindle horse that tests BR1-negative likely has chimerism or somatic mosaicism as the cause of the coat pattern. [Chimerism in Horses; Somatic Mosaicism in Horses]
- Incontinentia pigmenti (IP) is not detected by the BR1 test. IP is caused by a variant in the IKBKG gene (c.184C>T, OMIA:001899-9796), not MBTPS2. A mare with brindle-like striping and systemic findings (dental, hoof, skin lesion progression) who tests BR1-negative warrants evaluation for the IKBKG variant separately. [Incontinentia Pigmenti in Horses]
- The study was conducted in Quarter Horses. The BR1 variant was confirmed in a specific Quarter Horse family. Whether the same variant occurs in other breeds has not been systematically established. A brindle horse of a breed not represented in the Murgiano et al. study who tests positive has the variant; whether the variant behaves identically in a different genetic background has not been studied in the peer-reviewed literature.
The MBTPS2 gene: what it does
The MBTPS2 gene encodes Site-2 protease (S2P), a zinc metalloprotease embedded in the endoplasmic reticulum membrane. S2P is responsible for cleaving membrane-anchored transcription factor precursors, most importantly SREBP (sterol regulatory element-binding protein) and ATF6 (activating transcription factor 6), releasing their active forms into the nucleus where they regulate lipid metabolism and the unfolded protein response, respectively. [Murgiano et al. 2016]
Mutations in the human MBTPS2 orthologue cause three distinct genodermatoses: ichthyosis follicularis with atrichia and photophobia (IFAP syndrome), MEDNIK syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratoderma), and keratosis follicularis spinulosa decalvans (KFSD). All three involve skin and hair pathology in humans. The equine BR1 variant does not replicate these human conditions; the equine MBTPS2 mutation produces only the coat and hair-texture change with no systemic pathology reported. The study authors noted this discrepancy and attributed it to the partial rather than complete splicing disruption: approximately 80% of transcripts in BR1-affected horses retain correct splicing, which may be sufficient for normal function in other tissues. [Murgiano et al. 2016]
Practical summary for breeders
The BR1 test answers one specific question: does this horse carry the MBTPS2 c.1437+4T>C variant? If yes, the brindle pattern is heritable through X-linked transmission. If no, the pattern is likely not heritable. The test does not diagnose chimerism, mosaicism, or IP.
A summary of the breeding implications:
| Parent genotype | Offspring expectation |
|---|---|
| N/BR1 mare x N stallion | ~50% daughters N/BR1 (brindle coat); ~50% daughters N/N; ~50% sons BR1 hemizygous (sparse mane/tail, no stripe); ~50% sons N |
| N/N mare x BR1 stallion | All daughters N/BR1 (brindle coat expected); all sons N |
| N/N mare x N stallion | No BR1 offspring regardless of coat appearance of either parent |
The test is available from the UC Davis Veterinary Genetics Laboratory. Hair samples (pulled root-on, not cut) are the standard submission for equine coat-color genotyping.
Related reading
- Brindle Horses: Mechanisms, Genetics, and Patterns: the full framework: chimerism, mosaicism, BR1, IP
- The Genetics Behind Brindle Horses: the 2016 Murgiano study in detail: the variant, the splicing defect, the family
- Incontinentia Pigmenti in Horses: the IKBKG variant: when brindle stripes signal disease
- Blaschko’s Lines in Horses: why brindle stripes follow the body the way they do