Abortion and stillbirth (MIMT1-related)

 

Gene: MIMT1

Transmission: Autosomal dominant

Mutation: Imprinting error: 110 kb deletion in MIMT1 gene, a long non-coding RNA (lncRNA) gene.

Medical system: Fetal development

Breed: Ayrshire (Finnish)

Age of onset of symptoms: Late gestation, at birth

Abortions, stillbirths and embryonic lethality are problems for cattle production and the bovine artificial insemination industry.  They can be caused by numerous environmental, infectious, nutritional or genetic insults, either in isolation or in combination.

An Ayrshire insemination bull (YN51) in Finland was found to have a rate of late term lethality in its progeny of just under 50%.  Aborted foetuses or stillborn calves were about half normal weight but otherwise anatomically correct.  Molecular studies revealed that the bull had a 110 kb deletion in a region on chromosome 18 that is subject to maternal imprinting, that is to say that the region contains genes normally functional only when they are paternally derived and that maternally derived genes are inactivated.  Half of the bull’s progeny would be expected to receive the chromosome with the deletion and thus have no functional genes within the deleted region.  Further studies identified a non-coding RNA gene, MIMT1, to have its terminal sequences missing due to the deletion.  The MIMT1 gene is believed to be involved in regulating placental gene expression. Molecular studies of the parents of bull YN51 suggested that the deletion was a de novo mutation on YN51’s maternal copy of chromosome 18.  About 15% of YN51’s deletion carrying progeny were viable, likely due to incomplete maternal imprinting.   A DNA test is available to identify mutation carriers in YN51’s progeny so that these animals are not used for reproduction.

Other known genetic causes of abortion and embryonic lethality include:

ANXA10-linked, OMIA [2083-9913]

EXOSC4-linked, OMIA [2042-9913]

MED22-linked, OMIA [2043-9913]

MYH6-linked, OMIA [2039-9913]

OBFC1-linked, OMIA [2035-9913]

RABGGTB-linked, OMIA [2037-9913]

RNF20-linked, OMIA [2038-9913]

RPIA-linked, OMIA [2041-9913]

SNAPC4-linked, OMIA [2040-9913]

TTF1-linked, OMIA [2036-9913]

 

References:

OMIA link: [1565-9913]

Rutkowska K, Xu H, Flisikowski K. (2019) Differentially methylated region in bovine MIMT1 detected by small-scale whole-genome methylation sequencing.  [pm/31468362]

Xu H, Pausch H, Venhoranta H, et al. (2017) Maternal placenta modulates a deleterious fetal mutation.  Biol Reprod 97(2):249-257.  [pm/28679164]

Venhoranta H, Bauersachs S, Taponen J, et al. (2013) Fetal growth restriction caused by MIMT1 deletion alters brain transcriptome in cattle. Int J Dev Neurosci 31:463-7.  [pm/23726833]

Flisikowski K, Venhoranta H, Bauersachs S, et al. (2012) Truncation of MIMT1 gene in the PEG3 domain leads to major changes in placental gene expression and stillbirth in cattle. Biol Reprod 87:140.  [pm/23100617]

Flisikowski K, Venhoranta H, Nowacka-Woszuk J, et al. (2010) A novel mutation in the maternally imprinted PEG3 domain results in a loss of MIMT1 expression and causes abortions and stillbirths in cattle (Bos taurus). PLoS One 5:e15116.  [pm/21152099]

 

With contributions by: Nadia Faucher and Léonie Garneau, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).