LCORL

Expression Levels of LCORL Are Associated with Body Size in Horses.

"Genome-wide association analyses revealed the highest associated quantitative trait locus for height at the withers on horse chromosome (ECA) 3 upstream of the candidate gene LCORL.  The highly associated single nucleotide polymorphism BIEC2-808543 (-log(10)P = 8.3) and the adjacent gene LCORL [is] the most promising candidate for body size. We investigated the relative expression levels of LCORL and its two neighbouring genes NCAPG and DCAF16 using quantitative real-time PCR (RT-qPCR). We could demonstrate a significant association of the relative LCORL expression levels with the size of the horses and the BIEC2-808543 genotypes within and across horse breeds. In heterozygous C/T-horses expression levels of LCORL were significantly decreased by 40% and in homozygous C/C-horses by 56% relative to the smaller T/T-horses. Bioinformatic analyses indicated that this SNP T>C mutation is disrupting a putative binding site of the transcription factor TFIID which is important for the transcription process of genes involved in skeletal bone development. Thus, our findings suggest that expression levels of LCORL play a key role for body size within and across horse breeds and regulation of the expression of LCORL is associated with genetic variants of BIEC2-808543."

" the C allele of BIEC2-808543 is presumably the reason for the reduced expression of LCORL in larger sized horses. LCORL, also known as the Mblk1-related protein, shows characteristic motifs of transcription factors and analyses with mouse tissues indicate that it is able to activate transcription."<-So less LCORL equals greater height.

"In human genome-wide scans for adult stature evidences LCORL to be associated with trunk length and hip axis length"

"the correlation between growth of body and hair could be shown in various studies. The Rothmund-Thomson syndrome in human for example is characterized by severe dwarfism combined with an abnormal hair growth. Studies in mice revealed growth retardation in hair length and a retarded rate of body growth caused by the supply of high concentrations of the epidermal growth factor (EGF)"

So we can look at hair growth to find height genes.

"The candidate genes NCAPG and DCAF16 could be eliminated as candidates [for human height], whereas HMGA2 (high mobility group AT-hook 2, ECA6), ZFAT (zinc finger and AT hook domain containing, ECA9), LASP1 (LIM and SH3 protein 1, ECA11) could also possibly involved."

Four loci explain 83% of size variation in the horse.

"Unlike humans, which are naturally reproducing and possess many genetic variants with weak effects on size, we show that horses, like other domestic mammals, carry just a small number of size loci with alleles of large effect. Furthermore, three of our horse size loci contain the LCORL, HMGA2 and ZFAT genes that have previously been found to control human height. The LCORL/NCAPG locus is also implicated in cattle growth and HMGA2 is associated with dog size. Extreme size diversification is a hallmark of domestication."

"the immediately adjacent gene [to LCORL], NCAPG, has been implicated in prenatal growth"

"HMGA2 is an architectural transcription factor that regulates gene expression and directs cellular growth, proliferation and differentiation"

"1% of all human genes are now implicated in contributing to size variation"

Reaching new heights: insights into the genetics of human stature

"The height of an individual is the result of many growth and development processes and greater stature is not just a result of increasing bone length; tissue and organ sizes are usually also proportionately increased."

HMGA2 and GDF5 are two genes listed as highly influencing height.

LCORL along with c4orf30 are in the same gene loci as NCAPG.