Tag Archives: height genetics

SPIN4, new gene associated with overgrowth

The next study suggests that mechanisms that inhibit SPIN4 whether via gene therapy or supplements etc may be a way to enhance longitudinal bone growth. The next study is also by Jeffrey Baron who is huge in growth research.

A new genetic cause of overgrowth syndrome

“Pathogenic genetic variants in epigenetic regulatory proteins can cause overgrowth syndromes, such as Sotos syndrome due to mutations in NSD1 or Weaver syndrome due to mutations in EZH2. The identified genes encode DNA or histone methyltransferases, primarily serving as epigenetic writers. However, no overgrowth disorder has previously been described in a gene that acts primarily as an epigenetic reader{epigenetics are involved in delaying growth plate senescence so epigenetic alterations may keep growth plates open for longer}. We studied a 13-year-old male patient with generalized overgrowth of prenatal onset. His birth weight and length were 5.85 kg (+4.3 SDS) and 62 cm (+4.8 SDS), respectively. His height growth was striking at > +4 SDS without a significantly advanced bone age, eventually requiring epiphysiodesis at age 13 to reduce his adult height{I don’t know why they would do this with all the advantages of tall stature}. His timing of puberty was as expected. His biochemical studies, including IGF-1, were all negative. Karyotype, mutation analysis in NSD1 for Sotos syndrome, and chromosome 11p15 analysis (MLPA and methylation) for Beckwith-Wiedemann syndrome were normal. Furthermore, he had normal development and intelligence. His mother and maternal grandmother showed a significant height gain (+2 SDS gain) compared to their midparental height, suggesting an X-linked semi-dominant inheritance. Exome sequencing on the extended family identified a frameshift variant (NM_001012968.3, c.312_313AGdel) in Spindlin 4 (SPIN4), one of the epigenetic readers, with X-linked inheritance. Neither this variant nor any other loss-of-function variant in SPIN4 was present in a population database (gnomAD). In functional studies, we found evidence that SPIN4 binds specific histone modifications, promotes canonical WNT signaling, inhibits cell proliferation in vitro, and that the identified frameshift variant had lost all of these functions. Ablation of Spin4 in mice (either male or female) recapitulated the human phenotype with generalized overgrowth, including increased longitudinal bone growth{so SPIN4 inhibitors during development may stimulate longitudinal bone growth?}. Growth plate analysis revealed increased cell proliferation in the proliferative zone and an increased number of progenitor chondrocytes in the resting zone. We also found evidence of decreased canonical Wnt signaling in growth plate chondrocytes, providing a potential explanation for the increased number of resting zone chondrocytes. In conclusion, our findings provide strong evidence that SPIN4 is an epigenetic reader that negatively regulates mammalian body growth and that loss of SPIN4 causes an overgrowth syndrome in humans, expanding our knowledge of the epigenetic regulation of human growth.”

I can’t get this fully study yet but I will keep trying.

There’s not a lot of data on SPIN4 so this is really a novel finding. I also can’t find any research on compounds other than antibodies that inhibit SPIN4.

The Genetics Of Height

If we really wanted to get the ability to change our height and grow taller without going through the painful options of limb lengthening surgery, HGH daily injections, or crazy hours spent exercises, our only option may be some form of manipulation of our genetics. I am sure I have not considered all the options out there yet but eventually I believe I will be able to get through all the stuff.

I honestly believe that one man can accomplish this large task of taking all of the research and pathways of this very small niche of human endeavor and place it all in one place, one resource which you all can go to to learn about everything that is new that is being developed.

This is why I have decided also to devote a large portion of this website/ blog to discussing and analyzing genetics and possible genetic strategies to our goal of height increase. If any of you have ever studied genetics, whether in high school, college, or graduate school, I am sure a lot of the stuff is just review to you but please put up with me just for a short while until I get to the real stuff.

So let’s begin….

There is 23 chromosomes pairs in each of the nucleaus inside the cells of us humans. In each chromosome there are millions (or even billions) of nucleotidic base pairs that go together in 3 base pair codon groups that goes on (and collect together) to form our actual genes. The only job that these genes do is to make proteins. Referring to having a gene for a trait is no longer the scientifically accepted usage. In most cases, all people would have a gene for the trait in question, but certain people will have a specific allele of that gene, which results in the trait variant. Further, genes code for proteins, which might result in identifiable traits, but it is the gene, not the trait, which is inherited. (Reference Link)

From the scientific research done at Washington University at St. Louis it has already been shown that in terms of the social-anthropological concept of “race”, there is almost no difference between the so called labels which we have been putting on different looking people. We can organized and classified into groups like Hispanic, Latino, Black , African American, Native American, Middle Eastern, Asian, etc….

Well from the link HERE the conclusive results say that even though we have all of these phenotypical differences, we are essentially “exactly” the same and that the concept of “race” does not exist becasue the the geneticists who tried to find any specific gene that determines a “race” was never found. So the idea of race can not exist.

Well, one might then quick to ask “How does all this talk about race have anything to do with height?” Well, Race and height only has a weak correlation. When people make the comment like “asian people are short” or that “black people are big”, they are trying to link the anthropologically created concept of “race” and place a correlation of it with a phenotypical aspect of the group that they see.

Many people would be quick to then throw out a derision at such a politically incorrect statement however if we do look at the stats of say a chart of the average height of different nations around the world, we can sort of make a weak correlation. There is usually some small truth in the off of the cuff, unscientific statements made from just simple observation in our everyday life experience. Stereotypes exist for a reason. They are usually in the majority of the cases (like 51% of the time) true.

From the Wikipedia article on Race and Genetics found HERE,

“”A study by Tang et al. in 2005 used 326 genetic markers in order to determine genetic clusters. The 3,636 subjects involved in the study, from the United States and Taiwan, self-identified as belonging to white, African American, East Asian, or Hispanic (=self-identified race/ethnic group (SIRE)). The study found “nearly perfect correspondence between genetic cluster and SIRE for major ethnic groups living in the United States, with a discrepancy rate of only 0.14%.”[13] “”

I realize that it is only 1 study but let’s see that the implications are. The study implies that for all of our outer differences like skin color, nose shape, hair color, or other features that determine our “race”, we are still 99.9% exactly similar in our genome structure. (Note: I am not sure whether the 99.9 % similarity refers to the number of nuceotide base pairs in the genome or the number of number of genes, becasue the two numbers have a difference of  up to 5-6 magnitudes!) However, if we remember that our genome has over thousands of genes which are made of millions and billions of nucleotide base pairs, we realize that still means that there are a few genes out there will does determine our outer appearances.

The Human Genome Project which was completed in 2003 and the entire human genome was “supposedly” completed sequenced. That means that the basic infrastruture of the average human dna is understood. A good analogy is to think of each humans as each individual brand of car. The sequencing in a way allowed us to figure out in general, where each part of the car is supposed to be, and where to look if the car starts to have a problem. So the project allowed us to get a very good general idea on how the basic human genome and DNA structure is supposed to be laid out. However, in each individual, the genes will be slightly different, but only in say 0.1% of all the genes.

From the Human Genome Project website, I quote this passage

“”October 2004 findings from The International Human Genome Sequencing Consortium, led in the United States by the National Human Genome Research Institute (NHGRI) and the Department of Energy (DOE), reduce the estimated number of human protein-coding genes from 35,000 to only 20,000-25,000, a surprisingly low number for our species (7). Consortium researchers have confirmed the existence of 19,599 protein-coding genes in the human genome and identified another 2,188 DNA segments that are predicted to be protein-coding genes.

In 2003, estimates from gene-prediction programs suggested there might be 24,500 or fewer protein-coding genes (1). The Ensembl genome-annotation system estimates them at 23,299.

When analysis of the draft human genome sequence was published by the International Human Genome Sequencing Consortium on February 15, 2001, the paper estimated only about 30,000 to 40,000 protein-coding genes, much lower than previous estimates of about 100,000. This lower estimate came as a shock to many scientists because counting genes was viewed as a way of quantifying genetic complexity.

Studies since the publication of the draft genome sequence have generated widely different estimates. An analysis by scientists at Ohio State University suggested between 65,000 and 75,000 human genes (3), and another study published in Cell in August 2001 predicted a total of 42,000 (4).

Although the exact number of human genes is still uncertain, a winner of GeneSweep was announced in May 2003. GeneSweep was an informal gene-count betting pool that began at the 2000 Cold Spring Harbor Laboratory Genome Meeting. Bets ranged from around 26,000 to more than 150,000 genes. Since most gene-prediction programs were estimating the number of protein-coding genes at fewer than 30,000, GeneSweep officials decided to declare the contestant with the lowest bet (25,947 by Lee Rowen of the Institute of Systems Biology in Seattle) the winner (1). “”

So far the geneticists have found only 1 gene that has been shown to have some correlation to the height of the individual. However, the guess is that there is probably up to 20 specific genes that actually determine our height. What the research at the current time point at is that the height genes seem to be on the X chromosomes at numbers 7, 8, and 20 (remember that we have 23 chromosome pairs in each nucleus of our cells except red blood cells). In 2007, scientists did discover the 1st gene that showed to have an influence on one’s height after testing it through genetic manipulation on lab mice. That is the HMGA2 gene. Apparently, getting two of the “tall” type of the HMGA2 gene let’s one get an extra 1 cm in height compared to not having the gene. (Reference Link)

In conclusion, remember the study and search in genetics for the genes that determine height is still ongoing. I decided to post a last link that sums up very eloquently the effect that our genes have on our height, but also how it is connected to other factors.

“” Actually, height is what is called multifactorial. Not only are there many genes involved, such as genes for growth hormone, genes for the receptors on the outside of cells for growth hormone, genes for bone proportion, genes for the timing of the release of hormone and other growth factors; but there are also many interactions with the environment, including nutrition during gestation (while the mother was pregnant) and during the growth years, exposure to things such as cigarette smoke and alcohol before birth, birth order (generally second children are taller than first) and general health during the growth years. With all of these factors, it appears that we are born with a genetic potential for height (not all of the genes have been identified yet) and then the environment exerts its effects as we are growing. (reference link) “”

To get more information about the Human Genome Project, click HERE and HERE.