Genetics

A primer on genetics . This is not the main page! To return to the blog, click here.   I have a separate page discussing orientation.

Contents:


Genetics and orientation

Is it a choice, or is it hard-wired? Apparently it does make a difference to some people. Support for GLBT rights increases when people recognize that it's not a choice, leading to the loaded argument between terms like "sexual preference" and "sexual orientation". One post I read commented wryly, "my preference is to be tall; alas, my orientation is distinctly short." Like height, sexuality is a complex trait, which is not going to be completely determined by a single gene, or even several genes, but rather the interaction of multiple genes and the environment. Indeed, no geneticist buys a genetic determinism argument for complex traits. But since it keeps coming up, it might be worth a primer in genetics to explain why. In an extended series over the next couple of weeks, I will explain some basic genetics, and then address some of the issues that come up when we apply genetics to understanding sexual orientation.

As stated in this excellent LA Times op/ed,
Moreover, the empirical evidence for the role of genetics in human sexual orientation has been quietly but steadily mounting over the last 15 years. Studies of twins -- the mainstay of quantitative human genetics -- have been conducted on large populations in three countries. The results unambiguously demonstrate that heritability plays a major role in sexual orientation and far outweighs shared environmental factors such as education or parenting.
And in this news release from Stanford University,
Research into the biological basis of sexual orientation "presents a clear double message. Yes, genetics plays a part. No, it is not all genetics," Dora B. Goldstein, professor emeritus of molecular pharmacology, told the audience .... 
"This shouldn't be too surprising because that is what all kinds of behavioral studies indicate. Genes determine everything. The environment affects everything. Then there is this big area where the two interact," she added.
In 2014, a team of investigators reported that there is evidence in gay men for linkage of their sexuality to a genetic locus on the X chromosome.  Again,  this is not absolute -- nothing in complex traits is-- but provides further evidence for a genetic component that contributes to sexuality.

I'm focusing here on genetics, which is my field. For other general audience discussions of the science of orientation, there's a good article in NY magazine: The science of gaydar.  And for more detail in the discussion of genetics of human sexual orientation, here's a paper from Cambridge University (PDF).

Genetics Primer, 1: Variations on Mendel

If you ever took basic biology in school, you may remember the eye-color meme as an example of Mendelian genetics. Remember we have two copies of each of our genes, one from Mom, and one from Dad. The eye-color example is the one where they tell you that if you get at least one "B" gene from Mom OR Dad, you will have brown eyes (BB or Bb) but if you get the "b" version from both parents (bb) you will have blue eyes. Thus, blue eyed children can have brown eyed parents only if the parents are both carriers of the blue gene. In genetics, blue is recessive. So we all come away from this thinking that eye color is a simple Mendelian trait and is absolutely determined by the B/b versions we inherit.

BUT some people may remember that for this to work the teacher had to ignore the green eyed kids, or the hazel eyed kids. And occasionally there was a brown eyed kid who swore that both Mom and Dad have blue eyes, which the teacher skirted past very quickly (because she probably remembered that non-paternity rates in the US is as high as 10%, but that's not the only possibility). The fact is that there are multiple genes controlling eye color (hence the green and hazel eyes) and to strictly focus only on the B/b gene and the blue/brown binary is to ignore a lot of normal variation.

The simplification worked in the classroom only because variation in the other genes is more uncommon, especially in an ethnically uniform population, so teacher may have a fighting chance that a group of kids will fit the simple paradigm without having to invoke to greater complexity that actually exists. (Aside; the Mendelian inheritance is correct; it's how those genes are "read" into traits, or "phenotypes", that gets complicated.)

Even if you have blue eyes, there are variants from dull grey to brilliant blue, indicating that other factors affect the exact color formed. One complication is that there may be more than two versions of the gene (called "alleles"); not just B/b, but B1, B2, B3..... b1,b2 b3..... Even if any ONE person can have at most two versions of the gene, within the population there may be more. (I may be b1b2for example, and you may be b4b4, though we both have "blue" eyes). These different alleles are not present in equal numbers and may vary enormously in frequency; for example, in the population, b4 may be very common, and b2 may be extremely rare. And these may also change what we see in the person's traits.

Different genes can interact with each other and modify each other too. So, there may be other genes that affect only blue versus grey in the "bb" folks. And the green-eyed gene which we will call G is only visible if you have the blue eyed gene too (bb), if you have Brown (BB or Bb) then it doesn't matter what was at the green G/g site, it's masked. Just to complicate things further, you may have the gene for a particular color, but it may not be expressed for other reasons. Some of these reasons are genetic: for example, if you lack the gene to deposit thepigment in the proper place, it doesn't matter if you make the pigment. So people with BB or Bb alleles may not be brown eyed, due to other genes. And, some of these reasons are not strictly genetic, in the sense of being DNA-coded, such as epigenetic modification, variable penetrance, and variable expressivity--although they are often heritable. I'll discuss this later.

Depending on the trait (not just eye color), variation may be also be affected by the environment (for example the presence of particular chemicals in the diet), and some variation may simply occur by chance.

We tend to dislike this last explanation, because we like things to be determinate: black OR white (or blue OR brown); we don't like the idea that a random event (what the geneticists call "stochastic") can occur, and we don't like shades of gray. But chance also plays a part.

So, even for a trait as seemingly simple as eye color, we have already quite a lot of complication:
  • Multiple genes
  • Multiple versions of each gene (e,g, b1,b2, b3.....b(n))
  • Interactions between genes
  • Non-genetic changes (epigenetics, penetrance, expressivity)
  • Random variation
  • Environmental influence
Indeed the only deterministic thing we can say is that a bb child will not have brown eyes--- although I'm not sure even that is always true. The rest is up for grabs.

Genetics primer, 2: the role of chance

As we introduced with eye color, there may be random variation in the expression of a trait. Interestingly, a current theory of handedness suggests that this is exactly what happens for right handed versus left handed. Let's call the gene for Right handedness R, and the other version of this gene r. So, following our B/b diagram, we would suggest that RR or Rr people are right handed, and rr people are left handed. This works at first because we know that there is a genetic component to handedness in families.

But when you look in detail for that kind of inheritance, it doesn't work. There are still fewer left handed people than there should be, and there are some right handed people with left handed parents. What DOES fit the data is that "rr" isn't determinate of left handedness, it simply creates a random chance of either.

So the absence of R isn't "left", it's "either left or right determined at random". And again, potentially subject to modifiers in the environment, in the genome, and so on. Thus in two identical siblings, both rr, one can be left handed and one can be right handed simply by chance. There's still a genetic component, and they are still genetically identical, even though the outcome (the phenotype, in scientific terms) differs. Cool, isn't it?

One model suggests that this sort of characteristic is determined by a molecular mechanism to skew the distribution of daughter DNA molecules. Interestingly, there is a correlation with other asymmetrical characteristics, including left-right asymmetry in the brain, and the directionality of hair whorls on the crown of our heads. What's correlated is the asymmetry, not which way it worked out: that is, counterclockwise hair whorls are equally split between right and left handed people. So the counterclockwise whorl didn't influence your handedness; what they share is that both were determined randomly.

Oh, and the counterclockwise hair whorls may be more prevalent in gay men. Does this mean that if you are counterclockwise in hair, you are gay? No, nor does it mean that all gay men have counterclockwise hair whorls. But it might suggest there is some asymmetric component to sexuality, at least in men.

So you can see even in apparently simple human traits (eye color, handedness) there is a lot of complexity in how our genes are "read" and how they interact with and influence each other. And, we are not fully determined by our genetic information. Rather, genetics provides a palette but each of us is a unique painting that is a combination of genetics, environment, and chance. So, for complicated traits like behavior, you can predict that there will be a wide range of behaviors and they will be highly variable. All of which is perfectly "normal".


Genetics primer, 3:  epigenetics


Have you heard about epigenetics? (epi, from the Greek, means above or over). It's the hottest thing, these days. What is it? It's modifications of genetic information, that can be heritable even without changing the sequence of the DNA. And this state is transmitted by non-Mendelian rules.

What the heck does that mean?

First of all, we've already talked about Mendelian inheritance, using eye color: each parent gives you one of their two alleles for eye color, so you get a complete set of two.

Turns out that our genes are packaged in the cell with proteins called histones. The histones can be chemically modified in ways that affects the expression of the genes that are associated with them. These modifications can occur at targeted regions of the genome (meaning, at the position of certain genes). Or they can occur randomly. They can be influenced by external factors (like the environment). or they can be hard-wired, genetically encoded (which seems circular but there we are...them's the facts!). And mechanisms exist to maintain these modifications when cells divide, or even from generation to generation. So the information carried by the modified histones can be inherited.

These epigenetic changes are ways to fine tune the genome. They don't change the sequence of the underlying DNA, but they may change how it's used. So even identical twins with exactly the same DNA can have different epigenetic signals. One study showed that genetically identical rats raised by a mother who groomed them grew up to express genes differently than their twins who were raised by a mother who ignored them. Seems the rats that were groomed were laid back, and epigenetic modifications switched off stress genes. The ungroomed rats were stressed out and neurotic, with those genes turned on.

In some cases (called imprinting) the same gene inherited from one parent is expressed, whereas when inherited from the other parent, it isn't. In the diagram, the green box means the gene is expressed, and the red box means it is shut off. I. and II. are siblings who express the allele they got from dad, and repress (turn off) the allele they got from mom. Note that it doesn't matter that I. and II. are different sexes. They express the paternal version of this gene, and silence the one from mom.

If this were to happen with eye color (it doesn't, but lets pretend for a minute it does), it would mean that you "shut off" whatever allele you got from Mom. So if mom gave you B, and dad gave you b, you'd still be blue-eyed, because you shut off the B from mom. Even though genetically you are Bb, you are not expressing the B gene, so you look as though you are bb.

But if Dad gave you a B, you'd express it, and be brown eyed. Identical genotype: Bb. Different outcome, depending on which parent gave you the gene.

Where it gets gnarly is what happens in the next generation. If you are a man (individual I. in the diagram), when you make sperm, they will code both the version you got from your dad AND the version you got from your mom as "paternal", and expressible. Because to your child, either one is paternal, they got it from you. As shown in the diagram section III., all the sperm are recoded as paternal. However, if you are a woman, your eggs will recode both as maternal, so they will be turned off in the offspring--section IV of the diagram, all the eggs are recoded as maternal, regardless of the source of the allele.

Using my eye color example, either the B or the b would be active in your child--so even if you were blue eyed yourself, you could legitimately have a brown eyed child.

These effects are laid over the top of the palette of genes that we inherit. You can't switch off a gene you never inherited. Even if you inherit a gene, it doesn't necessarily mean you express it. And, if you don't inherit the capability to switch off a gene, it doesn't matter how much mom licks your ears.

There a great Nova episode on epigenetics for more information.

Genetics 4: orientation

Okay, now we have talked about how human traits are generally complex, and result from the interaction of multiple alleles, multiple genes, the environment, and random chance.

Let's apply these concepts to sexual orientation. It is estimated that some degree of homosexuality exists at about a 5-10% rate in the overall human population; it is found in all races and all societies, although depending on the social response, gay people may closet themselves for fear of exclusion, imprisonment, or death. Not all these people may identify strongly as gay or lesbian; sexuality is fluid and on a continuum. So probably about 2-5% of the population are more strongly homosexual. This persistence suggests that being gay is a fairly constant human variant, which can't be limited to a single environment or precipitating feature.

There is very good evidence for a genetic component of sexual orientation; in twin studies, the correlation of sexuality is way higher than its rate in the population (I've read as high as 50%), although it is not 100%. A lot of gay rights opponents say, "a-ha! if it were truly genetically determined, it would be 100%!" But this ignores the complexity that we discussed before; a geneticist would never expect something this complex to be 100% determinate; there is too much variation in the system. Even identical twins in a common environment are not identical for all traits which can be affected by random chance, imprinting, and epigenetics.  But this correlation is so very high, that it clearly indicates a strong genetic component to being gay.

Does this high correlation mean being gay is always inherited? Is there a single "gay gene"? No, not likely, and not necessarily for all gay people. Remember, in the interplay of genes, environment, and chance, the relative weight of any variable may differ from person to person. "Chance" may be a random mutation that was not present in the parents, (we are loaded with them), or a stochastic developmental pathway, as with handedness. Different combinations of different genes may contribute to a common outcome. It is likely that something as complex as sexual behavior has numerous inputs.

Consider the fruitfly, a workhorse of developmental genetics studies. Fruitflies are simple animals, behaviorally speaking. They don't live in large and complex social groups with diverse and complex behaviors. But even in the fruitfly, where sex is pretty hard wired, there are a number of genes that affect sexual behavior in diverse ways--some of which affect the wiring of the brain, others of which affect overall development of physical structures.

No one seems to have trouble recognizing that other characteristics are complex: think intelligence, or athletic prowess. We know that there are likely numerous genes that contribute to these, and that it's not simply genetic, although genetics makes a contribution. Why do some people have such a hard time with sexuality being just as complex?

So is there a component of environment? Possibly: there's a chemical environment in the womb, for example, and a psychological component in the family we grow up in. Gay men are more likely to have older brothers, for example. However, these are also variables, not absolutes, which occur on the background of the genetic variation we described. But it's not a simple cause-effect: you can't turn an infant gay by bathing them in hormones.

The genetic data are clear that there is a genetics component. It's not the whole story, necessarily, but it's certainly a big part of it.  Again, see this Cambridge University paper for more detail.  (PDF)

Genetics 5: traits on a continuum

In the case of sexuality, it is likely that we each exist on a continuum that runs from strictly gay to strictly straight. And it is clear that most people are towards one end or the other, though there is clearly a range, and for some people, sexual identity is more fluid than for others. This may be more true for women than men. (The biology of physical arousal is really different in women than men as well... something that's only recently become apparent as people are finally using female subjects. Women are not men, and our experience of sexuality is clearly quite different.)

The number of people who are overtly gay (as in, actively homosexual) is lower than the number who have a potential for homosexual behavior without acting on it (Hence the 2% vs 10% discrepancy). Interestingly, a substantial fraction of men who have sex with other men insist they are heterosexual.

The absolute middle position would be truly bisexual; the ones who do have a more conscious choice. Let me make a point here: many people opposed to gay-rights have a profound misunderstanding about bisexuality, thinking that bisexuals want simultaneous sexual partners ("threesomes"). This is NOT the case; a bisexual is simply someone who can orient their affections to either gender. If you have ever heard a man say, "I prefer redheads and blondes," that doesn't mean he expects to sleep with them both at the same time. It means he's likely to date either a red-head or a blonde, and not likely to be attracted to an olive-skinned brunette. Similarly, a bisexual may happily and monogamously date or marry a man or a woman. It's simply that their next date may be with someone of a different gender.

We see a range, or continuum in other traits too. Let's go back to handedness. Most of us are right handed, but it's a rare right handed person who can't do a few things with their left hand. For example, I'm right handed, but I can pour liquid from a container using either hand pretty well. And, some people are truly, completely ambidextrous and can use either hand interchangeably. (So the folks studying handedness don't use "right" and "left". They use "right" and "non-right".)

The majority of people who identify as gay or lesbian feel themselves oriented (not just sexually, but emotionally) towards a person of the same gender, and not making a conscious choice. After all, given the stigma that ranges from social disapproval in our society, to imprisonment, torture and execution of gays in some fundamentalist cultures, it is not clear why anyone would "choose" to be gay.

People can suppress their orientation, and try to "pass" as straight. We certainly all know of men and women who entered a straight marriage, had children, and tried to maintain a hetero life before finally admitting that wasn't who they are. In the past this led to a lot of misery (think of Larry Craig toe-tapping in the airport men's room, or conservative and anti-gay California legislator Roy Ashburn cruising gay bars). In our more enlightened age, young gays can grow up without trying to pretend and can be honest about their sexuality.

Genetics 6:How do traits persist?

Why does homosexuality persist in the population? If gay people are unlikely to have their own children, shouldn't this trait die out? Alternatively, as gay-rights opponents say "if everyone were gay the species would die out!" so if we accept gays, does that mean the demise of humanity?

Again, let us look at left-handedness. For many years, it was considered flatly wrong to be left handed. Indeed, the Latin root of "sinister" means "left" and people pointed to Biblical strictures against using the left hand. In some cultures, to use the left hand in public is an egregious insult. In my parents' generation, lefties were actually forced to use their right hands, often leading to cognitive and emotional problems; stuttering was a common side effect of this. We became more enlightened as a society and stopped forcing right-handedness on natural lefties; they do have some minor disadvantages (scissors, for example, are typically designed for the right hand) but we all co-exist perfectly happily together.

Okay, then why hasn't it died out? There is no strong selective disadvantage either; moreover, lots of right-handed people carry the gene that "allows" lefthandedness (R/r). And lefties are still able to have children at normal rates which keeps the trait present

A-HA, says the anti-gay-rights viewer, but there IS a disadvantage to being gay, they can't breed! Well, first of all, many gay people do have their own children, either from a previous straight marriage, or with a surrogate.  But even for childless gays, as long as any "gay genes" persist in relatives who have children without any disadvantage (think right handed people with Rr genotypes) then there is always a reservoir. And, if there is some advantage to the heterozygote, there can be positive selection in its favor. For example, some studies suggest that straight siblings of gay folks may have higher fertility than people without a gay relative. Simply put, there may be a significant advantage to having an uncle who doesn't have his own kids, because he contributes to the welfare of yours.

In fact, even a negative trait can have a positive selection. A great example is in the gene for sickle cell anemia, which predominantly affects people of African descent. This is a recessive gene such that affected individuals are aa in genotype; thus Mom and Dad were each Aa carriers. Interestingly, you would expect that this gene would have died out in a pre-medical age given the potential lethality of this disease, but it hasn't. Indeed, there is evidence that Aa carriers actually have an advantage because they are more resistant to malaria, and since 75% of their children, on average, will not be affected by the disease (they will be AA or Aa), this is sufficient positive selection to keep the gene present in the population. The a allele neither took over the population, nor died out.

So, an important point to remember is that "Sexual Selection" actually works at the level of a population, not at the level of an individual. For animals with complex societies, it is likely that there are multiple components working towards fitness, and sexual behavior is not limited to procreation but also plays a role in the relationships that are essential to survival (A great discussion of this is in Joan Roughgarden's excellent book, Evolution's Rainbow).

Just to push this further, if you have a complex family structure, it may be to the advantage of the group to have a few offspring to whose welfare many adults contribute--the gay uncle, in our own terms. But consider in a wolfpack, only one pair breeds while the others contribute to care for the pups. Or some species of birds, where a third adult helps the breeding pair raise the chicks.

So, traits can be selected in the population even when they don't improve the reproductive fitness of the individual.

Here's an excellent article from the New Scientist debunking the myth that natural selection can't explain homosexuality.

Genetics 7: Conclusions

The presence of homosexuality in all cultures and populations indicates that it is not simply a decadent western "choice". Additionally, same-sex behavior is well documented as a minority behavior throughout the animal kingdom; for example in domestic sheep, about 8-10% of rams are only interested in mounting other rams (and about an equal number are completely asexual, not interested in mounting rams or ewes). This can have significant economic impact on sheep farmers, but despite careful breeding and study, the trait persists.

So we see homosexuality very much like other complex traits, maintaining at a pretty constant level across time and populations. Which also shows us that the argument about humanity "dying out" is pretty, well, stupid. Straight people will continue to have kids. A few of those kids will continue to be gay. Since being gay is not a choice, the old canard about "recruiting" is based on ignorance.

The American Medical Association, the Psychiatric, Psychological , and Pediatric associations have all "de-pathologized" homosexuality. They consider homosexuality a normal human variation that in and of itself is not an illness or a sickness. It's a normal, if minority variant: like being a redhead, or a lefty. It doesn't hurt the people who have the trait, and it doesn't hurt the people who don't. Forcing people to deny it is harmful (and one of the reasons why the "Ex-gay movement" is so dangerous). This is another reason education is essential-- so people don't mistakenly try to cure the variant.

Gay folks are just as able as straights to make faithful and permanent commitments, and a big component of the marriage equality movement is to help people do so by providing the same social structures that support any marriage. After all, how stable do you think straight families would be without marriage? How faithful would young men be without this kind of structure? That's why in some disadvantaged communities, there is a strong movement to encourage marriage because of the support structures it provides struggling families.

What DOES cause problems for the gay community is marginalization and bias and bigotry. Fortunately for younger GLBT folks, things are a lot better than they used to be, but rejection of gay youth by their parents is still a major health issue and runaways and suicides are more likely to occur in gay kids. Let's hope we move to a point where we can be accepted simply as part of the wonderful varied tapestry of humanity, and not try to fit people into simple binaries.

A minority behavior is not wrong simply because it's the minority. It's not wrong to be red-headed, or left-handed.

So, what color are your eyes?

Reading list

There are a couple of excellent books for those interested in this topic. First is an exhaustive record of same-sex behavior in animals from fruit-flies to chimpanzees, Biological Exuberance by Bruce Bagemihl. HIs work shows how strongly observer bias leads to value-judgment interpretations, that are not scientific. The role of the scientist is to report the observtaions, not decide to ignore some of them because they don't fit a preconceived social notion of complementarity.

Second, Joan Roughgarden's book Evolution's Rainbow is a more detailed analysis of gender and sexuality in behavior. As she points out, many species have members fulfilling multiple distinct roles, not simply a sexual binary. Roughgarden also spends some time discussing varied sexual behaviors in mammals, including our cousin-primates, the chimpanzees. While I don't agree with all her points, which have a distinct agenda of her own, she offers much to think about.


Genetics Aside #1: bilateral gynandromorph

This is Sam, a chicken who is literally half male and half female. Early in Sam's development, Something Happened, (possibly a chromosomal nondisjunction, or a double fertilization). Sam is a mosaic, containing two types of cells; those with both ZZ chromosomes (male, in birds) or ZW (female) chromsoomes Sam's "male" half has more ZZ, and the "female" half has more ZW cells. And, the cells of each half developed autonomously : that is, it didn't matter what hormones were coursing through the body, all that mattered was the chromosomally determined sex of the individual cells.

In mammals, sex is presumed to be programmed during development, regardless of the chromosomal complement, in responses to signals from the developing gonad. This is called cell-nonautonomous, because the individual cells depend on external signals to "decide" which way to develop. So cells with male chromosomes can develop as females, if they get those signals. In birds, it appears to be somewhat different.

However, there is clearly some genetic determination in birds particularly for the gonad; alternatively, perhaps there is also some cell autonomous development of some traits in mammals. We'll talk more about sex determination next.

Aside #2: Chromosomes and Sex Determination

The conservatives have a rigidly deterministic view of biology. Sex seems pretty simple. Men are XY, women are XX. You get a Y chromosome from Dad, you're a boy. You get an X chromosome, you're a girl.

Mostly, but not always.

Due to disruptions in chromosome segregation, it's possible to be XYY. These individuals are male (and pretty indistinguishable from "normal" males; attempts to correlate extra Y chromosomes with violent behavior were discredited years ago).

XXY chromosomes give rise to Klinefelter's Syndrome. These patients are male, but generally have reduced testicular function and increased levels of female sex hormones. They are generally infertile.

By contrast, XXX females have relatively few symptoms and may not even be diagnosed.

It's possible to be XO--that is, one X chromosome only. Those with this "monosomy X" are female. It's called Turner Syndrome and is accompanied by a higher rate of cardiovascular and kidney abnormalities, and delayed puberty and infertility. (Women who are mosaics, that is only some of their cells lack the second X, are generally less severely affected).

But even if you are "normal" XY or XX, you may not be typically male or female. For example, you may be XY chromosomally, but phenotypically (that is, in appearance) female, if you have complete androgen insensitivity syndrome. That means a mutation in the gene required to respond to the masculinization effects of testosterone. The "default state" is to develop as a female. This may not be diagnosed till puberty, when failure to mature leads to diagnosis. These women generally identify as straight females.

That's just one example. There are many others where sex or gender are ambiguous for a variety of reasons. There are many ways to be biologically intersexed, sometimes with physical features of both sexes. It used to be that doctors at birth would decide "which sex" they thought an intersexed child should be, often with disastrous consequences. Increasingly, parents and intersexed individuals are demanding the right to be left alone and decide on their own gender identity as they grow up. In many cases, empowered young people decline the invasive surgeries that would make them more "normal," but this isn't true for everyone.

A now discredited view suggested that absent sex organs, a boy could be successfully raised as a girl, which was used to justify many "sex reassignment" surgeries of intersex children. The most famous victim of this was David Reimer, whose penis was accidentally cut off at circumcision. His parents were encouraged to raise him as a girl, but he was never happy in that identity and when he learned the truth, reverted to being a male. He died of suicide, ultimately unable to resolve the conflict between how he was forced to live growing up with who he was. And revolting abuses still continue, notably regarding girls who might be.... "less feminine."

Given this diversity, it's not surprising that gender identity is not necessarily a strict binary. It's also not surprising that some people identify as transgendered; just from these few examples, we can see that there's a wide range of biological reasons that may lead to differences in how someone feels about themselves, versus how they are "plumbed".

Isn't it about time that we stopped trying to put labels on people and shove them into strict boxes?

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