New York Cornell University research

[wonderboy]

http://www.nycornell.org/dermatology...rogenetic.html

[wonderboy]

bump

[clandestine]

Ok..

[534623]

http://www.nycornell.org/dermatology...rogenetic.html

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OUR RESEARCH

Our research team led by Dr. Animesh A. Sinha at the New York Presbyterian Hospital/ Weill Medical College of Cornell University is undertaking a non-profit research project involving the genetics of androgenetic alopecia (male-pattern baldness). This project, "Human Gene Expression Mapping in Skin Disease," is supported in part by grants from several non-profit organizations, and the study has been given Institutional Review Board approval.

Our experimental strategy is to use the most current molecular techniques to identify and study the genes responsible for androgenetic alopecia. We will analyze the expression of alopecia-related genes using "gene chips," a revolutionary technology that allows us to screen for thousands of genetic sequences simultaneously. Ultimately, we wish to find the links in the genome that render people susceptible to androgenetic alopecia. It is our short-term goal to gain a better understanding of why some individuals are pre-disposed to androgenetic alopecia and to identify those individuals at risk. Over the long term, our goal is to use this information to point us towards new and innovative therapies for androgenetic alopecia.

HOW YOU CAN HELP
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I really really like their intention and therefore I will try to help them with just 1 note:

GENE EXPRESSION (genetic information within cells and their niche) is always changing during your lifetime and is always influenced due to MANY factors.

Without such an always changing genetic behaviour (genes are basically "prone to" change), as just in very simple words described - something like "evolution of species" wouldn't happen.

I hope even laymen are able to understand these words.

For the future - the most important scientific approach would be rather to study all possibilities of how to REPLICATE the gene expression of the "permanent" donor area follicles - because simply replicating (aka "cloning") cells from donor area follicles, is DEFINITELY not the proper solution. To accomplish that, you simply have to find out what was there before the other appeared: The egg or the chicken first?
And if you have found the answer - try to find a way how to replicate the egg - or the chicken. lol

That thing, what was there first - THAT thingy contains the proper DNA for replication and THAT thingy doesn't change it's "genetic behaviour" as fast than the other thingy.

[wonderboy]

Sorry to bump it again, but I think that any thread
regarding androgenetic alopecia research should not
go away with so few replies :-)

[burtandernie]

Yeah I mean it sounds promising but they are asking for volunteers to be in the study so its going to be a pretty long time before anything from that shows up.

[534623]

HOW YOU CAN HELP
*************************

I really really like their intention and therefore I will try to help them with just 1 note:

GENE EXPRESSION (genetic information within cells and their niche) is always changing during your lifetime and is always influenced due to MANY factors.

Without such an always changing genetic behaviour (genes are basically "prone to" change), as just in very simple words described - something like "evolution of species" wouldn't happen.

I hope even laymen are able to understand these words.

For the future - the most important scientific approach would be rather to study all possibilities of how to REPLICATE the gene expression of the "permanent" donor area follicles - because simply replicating (aka "cloning") cells from donor area follicles, is DEFINITELY not the proper solution. To accomplish that, you simply have to find out what was there before the other appeared: The egg or the chicken first?
And if you have found the answer - try to find a way how to replicate the egg - or the chicken. lol

That thing, what was there first - THAT thingy contains the proper DNA for replication and THAT thingy doesn't change it's "genetic behaviour" as fast than the other thingy.

Yeah, and here are the "brand new" FACTS for my claims - and my suggestions/hints above ...

***********************************
http://www.ncbi.nlm.nih.gov/pubmed/23701444

Br J Dermatol. 2013 May 24. doi: 10.1111/bjd.12443.

Evidence for a polygenic contribution to androgenetic alopecia.
Heilmann S, Brockschmidt FF, Hillmer AM, Hanneken S, Eigelshoven S, Ludwig KU, Herold C, Mangold E, Becker T, Kruse R, Knapp M, Nöthen MM.
Source

Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Centre, University of Bonn, Bonn, Germany.

Abstract

BACKGROUND:

Male pattern baldness (androgenetic alopecia, AGA) is a highly heritable trait and the most common form of hair loss in humans. Eight genome-wide significant risk loci for AGA have been identified.
OBJECTIVES:

To determine whether a polygenic component contributes to the genetic risk for AGA.

METHODS:

This study used a German case-control sample for AGA, which comprised 581 severely affected patients and 617 controls, to determine the contribution of polygenic variance to AGA risk. The sample was divided evenly into discovery and test samples. An additive polygenic risk score was calculated from risk alleles with increasingly liberal P-values in the discovery dataset, which was then used to test for the enrichment of AGA risk score alleles in the independent test samples.

RESULTS:

The polygenic score analysis provided significant evidence for a polygenic contribution to AGA where the amount of variance explained was 1.4-4.5%.

CONCLUSION:

This study provides evidence for the specific contribution of a polygenic component to the overall heritable risk for AGA. To some degree, the polygenic architecture of AGA might reflect the complexity of the biological pathways involved. Further analyses and strategies that complement conventional genome-wide association studies are needed to identify these factors. These may include pathway-based analyses, the analysis of functional candidate genes and tests for epistatic effects with known loci.
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Okay, so what exactly does "highly heritable trait" mean?

You can find, for example, the simple version at Wikipedia, to get a clue:
***************************
Heritability
The heritability of a population is the proportion of observable differences between individuals that is due to genetic differences.

Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics (in their "phenotypes"). Heritability thus analyzes the relative contributions of differences in genetic and non-genetic factors to the total phenotypic variance in a population. For instance, some humans in a population are taller than others; heritability attempts to identify how much genetics are playing a role in part of the population being extra tall.
***************************

Anyway, concerning "AGA" - what exactly does it mean all in all?

Even if you find a way to replicate "THE proper source" in the lab (on synthetic basis etc etc etc), the replicated "proper source" wouldn't really work, of course, for everyone or every (AGA-)patient. And that means, if you have found something (a proper technology etc) how to replicate THE proper source (e.g. to get hair follicles to grow properly/correct at all), you have to do it, of course, "patient-specific". And that means -provided, you have found proper solutions/technologies to accomplish that at all- the procedures per se would/could be very very costly, because THE proper solution (replication of the THE source) ISN'T as "simple" as cloning some cells in the lab ...

[Westonci]

I wish I lived in New York so I could participate in the research

[Desmond84]

Yeah, and here are the "brand new" FACTS for my claims - and my suggestions/hints above ...

***********************************
http://www.ncbi.nlm.nih.gov/pubmed/23701444

Br J Dermatol. 2013 May 24. doi: 10.1111/bjd.12443.

Evidence for a polygenic contribution to androgenetic alopecia.
Heilmann S, Brockschmidt FF, Hillmer AM, Hanneken S, Eigelshoven S, Ludwig KU, Herold C, Mangold E, Becker T, Kruse R, Knapp M, Nöthen MM.
Source

Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Centre, University of Bonn, Bonn, Germany.

Abstract

BACKGROUND:

Male pattern baldness (androgenetic alopecia, AGA) is a highly heritable trait and the most common form of hair loss in humans. Eight genome-wide significant risk loci for AGA have been identified.
OBJECTIVES:

To determine whether a polygenic component contributes to the genetic risk for AGA.

METHODS:

This study used a German case-control sample for AGA, which comprised 581 severely affected patients and 617 controls, to determine the contribution of polygenic variance to AGA risk. The sample was divided evenly into discovery and test samples. An additive polygenic risk score was calculated from risk alleles with increasingly liberal P-values in the discovery dataset, which was then used to test for the enrichment of AGA risk score alleles in the independent test samples.

RESULTS:

The polygenic score analysis provided significant evidence for a polygenic contribution to AGA where the amount of variance explained was 1.4-4.5%.

CONCLUSION:

This study provides evidence for the specific contribution of a polygenic component to the overall heritable risk for AGA. To some degree, the polygenic architecture of AGA might reflect the complexity of the biological pathways involved. Further analyses and strategies that complement conventional genome-wide association studies are needed to identify these factors. These may include pathway-based analyses, the analysis of functional candidate genes and tests for epistatic effects with known loci.
*************************

Okay, so what exactly does "highly heritable trait" mean?

You can find, for example, the simple version at Wikipedia, to get a clue:
***************************
Heritability
The heritability of a population is the proportion of observable differences between individuals that is due to genetic differences.

Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics (in their "phenotypes"). Heritability thus analyzes the relative contributions of differences in genetic and non-genetic factors to the total phenotypic variance in a population. For instance, some humans in a population are taller than others; heritability attempts to identify how much genetics are playing a role in part of the population being extra tall.
***************************

Anyway, concerning "AGA" - what exactly does it mean all in all?

Even if you find a way to replicate "THE proper source" in the lab (on synthetic basis etc etc etc), the replicated "proper source" wouldn't really work, of course, for everyone or every (AGA-)patient. And that means, if you have found something (a proper technology etc) how to replicate THE proper source (e.g. to get hair follicles to grow properly/correct at all), you have to do it, of course, "patient-specific". And that means -provided, you have found proper solutions/technologies to accomplish that at all- the procedures per se would/could be very very costly, because THE proper solution (replication of the THE source) ISN'T as "simple" as cloning some cells in the lab ...

Very solid argument by Iron_Man that deserves a great deal of discussion.

It is important to differentiate between TWO approaches to achieve follicular neogenesis:

1) To use the existing scaffold, structures and stem cells present in the balding zone to 're-start' the hair follicles that went into dormancy, or

2) To engineer new follicles based on non-AGA hair follicles from the donor zone.

These are TWO fundamentally different approaches and it's noteworthy to point out that the source of building blocks used to create these follicles will decide the success of such a novel therapy.

On one hand, you are using stem cells and structures from the balding areas (as was the case with Aderans & Replicel) to kickstart the follicular growth once more, which will most likely lead you to no where as was evident with Aderans trials. The reason being is all the complex polygenic factors that must be corrected in order for terminal hairs to sprout and cycle. Problems ranging from the tendency for DP cells in the AGA zone to express 3-4 times the numbers of androgen receptors down to specific details such as promoters of inflammatory cascade and fibrosis that are present in balding areas.

On the other hand, you have the blueprint for a perfectly functioning hair follicle that will continue to cycle throughout the person's lifetime with an almost absent receptorship for androgens. This blueprint is in the horse-shoe pattern zone.

So, it would be blatantly obvious to any scientist that engineering a follicle from such blueprint would be far easier than the behemoth task of solving all the polygenic conundrums.

This is the reason why the work being conducted by teams such as Tsuji lab is far more important to anyone suffering from hairloss than other Bio-labs that have mistakenly chosen the first path to combat such a complex and mysterious genetic conundrum.