Design and the Brain

[Beccs]

Mark, you seem really confused.

Atheism and evolution are two different things. Atheism and common descent are two different things. Atheism and science are two different things.

You keep conflating atheism with all these other things and its getting you nowhere. Maybe if you learned to focus on the right thing, you'd get somewhere.

And P.S.: Evolution, including common descent, is still an applied science. It ain't going away.

Quoted for truth.

 

[mark kennedy]

I don't now (nor did I previously) have time for a complete response to your posts Mark, but might I say I am glad to see I have goaded you into admitting the truth, that it is all about God, and stop the silly nonsense derived from your complete lack of understanding of biology. Good to see.

Really? Here's some basic Biology for you:

Single-base substitutions are most apt to occur when DNA is being copied; for eukaryotes that means during S phase of the cell cycle.

No process is 100% accurate. Even the most highly skilled typist will introduce errors when copying a manuscript. So it is with DNA replication. Like a conscientious typist, the cell does proofread the accuracy of its copy. But, even so, errors slip through.

It has been estimated that in humans and other mammals, uncorrected errors (= mutations) occur at the rate of about 1 in every 50 million (5 x 10^7) nucleotides added to the chain. (Not bad — I wish that I could type so accurately.) But with 6 x 10^6 base pairs in a human cell, that mean that each new cell contains some 120 new mutations. Frequency of Mutations​

Now compare that to genetic differences between chimpanzees and humans:

Sakaki said their analysis found about 68,000 insertions or deletions. "That is almost one insertion/deletion every 470 bases," he said. In addition, a small proportion of genes showed a relatively higher rate of evolution than most other genes. "We haven't known what proportion of the genes shows adaptive evolution. This study shows it to be about 2 to 3%," he said. Chimps are not like humans (28 May 2004)
Whole-chromosome comparison reveals much greater genetic differences than expected​

So which is it, 1 in 50 million bases or 1 for every 470?

And you keep forgetting to say "have a nice day". I'm not getting to you am I?

Have a nice day Mark

Have a nice day
Mark

 

[RealityCheck]

It has been estimated that in humans and other mammals, uncorrected errors (= mutations) occur at the rate of about 1 in every 50 million (5 x 10^7) nucleotides added to the chain. (Not bad — I wish that I could type so accurately.) But with 6 x 10^6 base pairs in a human cell, that mean that each new cell contains some 120 new mutations. Frequency of Mutations

Here, the article is talking about copying errors from one human cell to another. This is within a single human - that is, when your cells replicate, there are copying errors every time.

That's your apple. Now for your orange.

Now compare that to genetic differences between chimpanzees and humans:

Sakaki said their analysis found about 68,000 insertions or deletions. "That is almost one insertion/deletion every 470 bases," he said. In addition, a small proportion of genes showed a relatively higher rate of evolution than most other genes. "We haven't known what proportion of the genes shows adaptive evolution. This study shows it to be about 2 to 3%," he said.​

That's comparing differences between chimps and humans? How can you compare that to cellular replication within a single human?


​

 

[KCfromNC]

My side has proclaimed the Gospel to pagan emperors in Rome and were tortured and murdered, then Rome fell. For a thousand years Christian theology was queen of the sciences and natural science thrived.

You're saying the dark ages (say, 400 to 1400CE) were the best that "Christian" science can do. Wow, convincing argument for the superiority of that approach to investigating the natural world. What was the life expectancy in say, 1000AD compared to 2000AD? Which set of medical science would you rather be the victim, er, patient of?

When Christianity was still celebrated and embraced here in the States our educational system was as good as anyones. Now the Darwinians want to indoctrinate every child from preschool on into the atheistic/materialistic philosophy and our public schools can't teach anything well.

Post hoc ergo propter hoc, to say the least. It's just as valid as saying "When Christianity was still celebrated and embraced here in the States minorities and immigrants were legally discriminated against and even killed with the implicit knowledge of the government. Now that evolution is being taught in school, we're finally embracing the equality that our founders envisioned."

Got a newsflash for you, my side has been overturning pagan mythographers for thousands of years.

Overturning, coopting, same difference.

Your side just comes along and pretends they have been there all along. You haven't really, maybe 150 years at best.

The modern scientific method is a bit older than that, but you're only off by a factor of 2 or 3. And interestingly enough, the advent of this method corresponds to an increase in life expectancy, standard of living, and knowledge & education of people around the world. Seems that the Christian theocracies that preceded it (and that you wish to return to) weren't so hot after all.

 

[Blayz]

Really? Here's some basic Biology for you:

It has been estimated that in humans and other mammals, uncorrected errors (= mutations) occur at the rate of about 1 in every 50 million (5 x 10^7) nucleotides added to the chain. (Not bad — I wish that I could type so accurately.) But with 6 x 10^6 base pairs in a human cell

You meant 6 x 10^9, yes? 6 billion, not 6 million.

that mean that each new cell contains some 120 new mutations. Frequency of Mutations
Now compare that to genetic differences between chimpanzees and humans:
Sakaki said their analysis found about 68,000 insertions or deletions. "That is almost one insertion/deletion every 470 bases," he said. In addition, a small proportion of genes showed a relatively higher rate of evolution than most other genes. "We haven't known what proportion of the genes shows adaptive evolution. This study shows it to be about 2 to 3%," he said. Chimps are not like humans (28 May 2004)
Whole-chromosome comparison reveals much greater genetic differences than expected
So which is it, 1 in 50 million bases or 1 for every 470?

Its both Mark, since one measures the mutation rate for a single cell replication and the other the fixed differences between two species. Once again, you fail to take population into account. But since its close to Xmas, here's a present for you, a fact I am sure you will be able to twist into some fundy anti evolution nonsense. A single nucleotide polymorphism exists in humans at a rate of about 1 change every 1000bp. In other words, the average sequence of one person (to account for the 120 changes per cell) compared to another will differ by 0.1%, or 3 million base pairs.

How kewl is that? Now you can not only confuse and conflate the 1/50 million for dna pol errors, and the 1 in 470 for human/chimp dfference (or whatever number you like to derive from the 5 million/35 million diferences), but also a 1/1000 per person!

Have a nice day
Mark

You too mate, you too. I sincerely hope you get enough loin girding and rhetoric avoidance techniques to actually do this study you keep threatening us with. You aint getting any younger!

 

[NailsII]

Got a newsflash for you, my side has been overturning pagan mythographers for thousands of years.

Overturning or plagerising?

 

[mark kennedy]

You meant 6 x 10^9, yes? 6 billion, not 6 million.

You would have to ask Dr. Kimball, that is a quote from his Biology pages.

Its both Mark, since one measures the mutation rate for a single cell replication and the other the fixed differences between two species. Once again, you fail to take population into account. But since its close to Xmas, here's a present for you, a fact I am sure you will be able to twist into some fundy anti evolution nonsense. A single nucleotide polymorphism exists in humans at a rate of about 1 change every 1000bp. In other words, the average sequence of one person (to account for the 120 changes per cell) compared to another will differ by 0.1%, or 3 million base pairs.

Populations of humans now are well in the billions and we all differ by less then 1% of our DNA. Ancestral human and ape populations are usually estimated anywhere between 10,000 and 100,000 with prehistoric populations being isolated in equatorial Africa until about 1 million years ago.

How kewl is that? Now you can not only confuse and conflate the 1/50 million for dna pol errors, and the 1 in 470 for human/chimp dfference (or whatever number you like to derive from the 5 million/35 million diferences), but also a 1/1000 per person!

The divergence exceeds any known mutation rate for 5 million years. In order for the mutations to be inheritable they would have to be germline mutations. So that comes to 20 indels and 140 single base substitutions every 20 year generation. For a 1.33% divergence you are looking at a mutation rate of 2.5 x 10^-8 for a population average of 10,000, for 100,000 it's 1.5 x 10^-8. You multiply that by 5 time in order to get what the mutation rate would have had to be for the last 5 million years.

You too mate, you too. I sincerely hope you get enough loin girding and rhetoric avoidance techniques to actually do this study you keep threatening us with. You aint getting any younger!

Your telling me, I'm full time Army right now so college is on hold for the time being. These debates keep me amused when I really have nothing better to do but they rarely go anywhere. I listen to the MIT open courseware and while interesting it is certainly not the same. I'm a Liberal Arts major so I'll need a couple of science classes for that.

Have a nice day
Mark

 

[FishFace]

Really? Here's some basic Biology for you:

Single-base substitutions are most apt to occur when DNA is being copied; for eukaryotes that means during S phase of the cell cycle.

No process is 100% accurate. Even the most highly skilled typist will introduce errors when copying a manuscript. So it is with DNA replication. Like a conscientious typist, the cell does proofread the accuracy of its copy. But, even so, errors slip through.

It has been estimated that in humans and other mammals, uncorrected errors (= mutations) occur at the rate of about 1 in every 50 million (5 x 10^7) nucleotides added to the chain. (Not bad — I wish that I could type so accurately.) But with 6 x 10^6 base pairs in a human cell, that mean that each new cell contains some 120 new mutations. Frequency of Mutations​

Now compare that to genetic differences between chimpanzees and humans:

Sakaki said their analysis found about 68,000 insertions or deletions. "That is almost one insertion/deletion every 470 bases," he said. In addition, a small proportion of genes showed a relatively higher rate of evolution than most other genes. "We haven't known what proportion of the genes shows adaptive evolution. This study shows it to be about 2 to 3%," he said. Chimps are not like humans (28 May 2004)
Whole-chromosome comparison reveals much greater genetic differences than expected​

So which is it, 1 in 50 million bases or 1 for every 470?

120 mutations per generation * 5 million years / 20 years per generation = 30,000,000 differences between chimps and humans if every single mutation were fixed.

Apparently, 0.2% of mutations were fixed, if the figures you quoted were accurate.

Have a nice day
Mark

You too.

ETA: Shall we add this to the list of errors you're not admitting to, or are you going to be honest about this one?

 

[mark kennedy]

120 mutations per generation * 5 million years / 20 years per generation = 30,000,000 differences between chimps and humans if every single mutation were fixed.

Apparently, 0.2% of mutations were fixed, if the figures you quoted were accurate.

As usual you are utterly confused, if the comparison of the two genomes is any indication these are the changes:

35 million single base pairs (MB) and 5 million indels totaling 90 MB. That comes to 40,000,000 differences and does not include the 8 chromosomal rearrangements from 2 MB to 4 MB totaling about 20 MB. That means 1 indel and 7 single base substitutions permanently fixed per year of 5 million years. For an average population of 10,000 the mutation rate comes to 2.5 x 10^-8. For a population of 100,000 it's 1.5 x 10^-8. That's a 1.33% divergence and the mutation rate for all mutations are about 2.5 x 10^-8 now multiply that by 5x.

ETA: Shall we add this to the list of errors you're not admitting to, or are you going to be honest about this one?

Let's see if we can get this back on topic despite your constant efforts to derail it. You already have no clue how the highly conserved regulatory gene involved in the Cajal–Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. Now let's talk about what happens when highly conserved genes involved in neural functions change:

The most frequent chromosomal abnormality seen in autism populations involves duplication of sequences in a region on the proximal part of the long arm of chromosome 15, specifically the interval 15q11-q13. These duplications typically take one of two forms: (1) tandem duplication of a 4–5 million base-pair (Mb) region corresponding to 15q11-q13, or (2) supernumerary pseudodicentric, inverted, and duplicated regions of chromosome 15 [so-called inv dup(15) or idic(15) marker chromosomes] that now contain two additional copies of a larger region. These duplications are associated with substantial risk for autism when derived from maternal but not paternal chromosomes. This parental-specific association suggests a genomic imprinting effect and makes relevant consideration of two disorders that result from interstitial deletion of the same 15q11-q13 region. Genetics of Childhood Disorders: Duplication and Inherited Susepibility of Chromoseom 15q11-q13 Genes in Autism by James Sutcliffe and Erika Nurmi​

Here is another one:

To understand the molecular biology of fragile X syndrome, it is useful to review the changes in the brains of affected individuals. Overall, autopsy analyses reveal few light microscopic changes. Higher-resolution analysis with electron microscopy shows that the dendritic spines from fragile X patients are abnormal. They are morphologically similar to the spines of immature, developing brains. The dendritic spines in fragile X individuals are long and thin compared with the short and broad spines of mature cortical neurons (Fig. 1).
We know that neurogenesis and neuronal migration proceed normally in fragile X individuals, suggesting that the pathology occurs later, during synaptic maturation. Apparently, the protein affected by fragile X syndrome or proteins that depend on this protein are necessary for proper synaptic growth and maturation. We now turn to how this story unfolded over the past decade through advances in molecular biology.
Fragile X syndrome is the most common form of inherited mental retardation. It occurs with a frequency of approximately 1:4,000 in males and 1:8,000 in females. The fragile X mental retardation-1 (FMR1) gene was cloned more than a decade ago—a major accomplishment. Characterization of the mutation revealed a novel type of genetic mutation called a triplet repeat expansion. This type of mutation was originally identified in Huntington chorea. When the FMR1 gene was sequenced, and proved to be second example of a triplet repeat expansion, genetic researchers realized that they had discovered a new type of mutation. Since then, triplet repeat expansions have been described in approximately a dozen neuropsychiatric disorders. Genetics of Childhood Disorders, Fragile X Syndrome by Paul J. Lombroso, M.D​

The examples of deleterious affects on neural functions are legion and not one example of a beneficial affect to be had. I'm not limiting myself to goddidit and goddidntdoit clutch phrases. I want to know what must have happened, the best way to know that is to learn how species are limited by the deleterious affects of mutations.

 

[Naraoia]

Now let's talk about what happens when highly conserved genes involved in neural functions change: [...examples...]

You do realise that, especially in the autism case, your examples are talking about large-scale duplications and not point mutations? Besides, you are also talking about protein-coding genes, while your pet brain gene is an RNA gene.

Please come up with relevant examples.

And again, you have not shown that a mutation in such genes cannot be beneficial.

 

[Pete Harcoff]

I don't want evolution to go away, or common descent. Creationism is radical evolution, I am just looking for the directly observed and demonstrated genetic mechanisms for adaptive evolution. You led me on to one the other day and you guys always do, you just have no clue what I'm actually doing here.

I'm studying two things, genetic mechanisms for adaptive evolution and TOE zealots. I am most interested in the former but if I'm ever going to study this formally I will need to know a lot about the latter and how to avoid their rhetorical traps.

If you want to talk about various biology related stuff to human/chimp ancestry than just talk about that. On the other hand, you periodically launch into these diatribes about some sort of atheistic/Darwinist/secular/kitchensink conspiracy theory. Which is a little too "tinfoil hat" for my books.

 

[mark kennedy]

You do realise that, especially in the autism case, your examples are talking about large-scale duplications and not point mutations? Besides, you are also talking about protein-coding genes, while your pet brain gene is an RNA gene.

Please come up with relevant examples.

You act as if that is difficult:

The p53 tumor suppressor is implicated in cell cycle control, DNA repair, replicative senescence and programmed cell death. Inactivation of the p53 contributes to the wide range of human tumors, including glial neoplasms. In this review, we describe the regulation and biochemical properties of p53 protein that may explain its ability to activate various genetic programs underlying cellular responses to stress conditions. The overall spectrum of p53 mutations is rather shared between tumor types indicating that these mutations are not tumor type-specific. However, there is one example of germ-line mutation of p53 gene (the deletion of the codon 236) that is associated with a familiar brain tumor syndrome. We compare the frequency and type of most common mutations among various brain tumours (focusing on glioblastomas) and their consequences on protein functions. Furthermore, we discuss the most promising approaches of potential brain tumor therapy, including an adenovirus-mediated p53 gene transfer. Human glioblastomas are highly sensitive to the effects of p53 activity when the wild-type p53 is introduced ectopically. It suggests that the genetic or pharmacological modulation of the p53 pathway is potentially important strategy in the treatment of human cancers. The diversity of p53 mutations among human brain tumors and their functional consequences​

How about the PDYN gene? Diseases and Mutations in which this Gene is Involved include but are not limited to:
Epilepsy temporal lobe, Hyperalgesia, Epilepsy, Parkinson disease, Absence seizures and Schizophrenia

PNYN Gene Card

To find evidence of regulatory changes underlying uniquely human traits, Rockman et al. examined the regulatory evolution of prodynorphin, a gene expressed in multiple brain and endocrine cell types. The protein encoded by prodynorphin is a precursor molecule for a suite of neuropeptides that bind to opiate receptors and affect perception, pain sensation, emotion, and learning. In humans, prodynorphin's promoter contains what's called a 68 base-pair tandem repeat polymorphism—individuals can have up to four copies of the 68 DNA base-pair element, which occur side by side. The polymorphism, which affects how many transcripts of the gene are produced, has been tentatively linked to schizophrenia, cocaine addiction, and epilepsy.

To explore how this functional variation evolved, Rockman et al. first sequenced and analyzed prodynorphin regulatory DNA from 74 human chromosomes and 32 nonhuman primate chromosomes (chimp, bonobo, gorilla, orangutan, baboon, and two macaque species). The duplication leading to tandem repeats appears unique to humans, since all the monkeys and other great apes carry only one copy of the 68 base-pair element. Further distinguishing humans from the last common ancestor of humans and chimps, the human copies also carry five mutations, or substitutions, far more than would be expected if the mutations were neutral (that is, had no effect on fitness). Three nearby polymorphisms also occurred at a higher-than-expected frequency in humans, a sign that selection acted on the linked neighboring sequences. The protein-coding sequence of prodynorphin, on the other hand, appears to have undergone negative selection, discarding harmful mutations that would disrupt its function.​

(2005) Selection on a Neural Gene Regulator Sheds Light on Human Evolution. PLoS Biol

And again, you have not shown that a mutation in such genes cannot be beneficial.

What I have demonstrated repeatedly is the the only known affect of mutations on the development of the human brain is deleterious. Counter evidence is often invited but never provided, the obvious reason is that it just does not happen. What is being demonstrated is what would have had to happen for the human brain to evolve from that of apes.

 

[Pete Harcoff]

Counter evidence is often invited but never provided, the obvious reason is that it just does not happen.

Or the most obvious reason given the relatively rarity of beneficial mutations combined with the logistical difficulties in screening for such mutations means they just haven't been found yet.

 

[mark kennedy]

Or the most obvious reason given the relatively rarity of beneficial mutations combined with the logistical difficulties in screening for such mutations means they just haven't been found yet.

On the contrary, the is abundant evidence that neural genes for humans are unique and highly conserved.

To explore how this functional variation evolved, Rockman et al. first sequenced and analyzed prodynorphin regulatory DNA from 74 human chromosomes and 32 nonhuman primate chromosomes (chimp, bonobo, gorilla, orangutan, baboon, and two macaque species). The duplication leading to tandem repeats appears unique to humans, since all the monkeys and other great apes carry only one copy of the 68 base-pair element. Further distinguishing humans from the last common ancestor of humans and chimps, the human copies also carry five mutations, or substitutions, far more than would be expected if the mutations were neutral (that is, had no effect on fitness). Three nearby polymorphisms also occurred at a higher-than-expected frequency in humans, a sign that selection acted on the linked neighboring sequences. The protein-coding sequence of prodynorphin, on the other hand, appears to have undergone negative selection, discarding harmful mutations that would disrupt its function.[/indent]

(2005) Selection on a Neural Gene Regulator Sheds Light on Human Evolution. PLoS Biol

We know what results from mutations in the gene. Diseases and disorders like; Epilepsy temporal lobe, Hyperalgesia, Epilepsy, Parkinson disease, Absence seizures and Schizophrenia.

 

[Naraoia]

You act as if that is difficult:

Please dear, if you argue a point then it is you who must come up with relevant supporting examples. I'm not acting as if that's difficult, I'm acting as if you've not done your job.

Ok, the infamous P53 sort-of fits. (Though it's still not an RNA gene, as you may have noticed...)

How about the PDYN gene? Diseases and Mutations in which this Gene is Involved include but are not limited to:
Epilepsy temporal lobe, Hyperalgesia, Epilepsy, Parkinson disease, Absence seizures and Schizophrenia

And the mutations you quote are tandem repeat polymorphisms. Of 68 bases. Hardly a point mutation. Might be called a large indel but it's certainly not on the scale of the mutations in the brainy gene you were originally talking about.

Besides, it's still not an RNA gene. (Which is perhaps the lesser of my peeves, but still, if you want to say something about an RNA gene then please support what you say with RNA gene examples if at all possible)

What I have demonstrated repeatedly is the the only known affect of mutations on the development of the human brain is deleterious. Counter evidence is often invited but never provided, the obvious reason is that it just does not happen. What is being demonstrated is what would have had to happen for the human brain to evolve from that of apes.

No, you have given examples of deleterious mutations (most of which were pretty large ones). If you could cite, say, a respectable enough review article or database thing or something that says there are no known beneficial mutations and provides some support other than a few genetic diseases I'd be more inclined not to dismiss your argument.

 

[Pete Harcoff]

We know what results from mutations in the gene. Diseases and disorders like; Epilepsy temporal lobe, Hyperalgesia, Epilepsy, Parkinson disease, Absence seizures and Schizophrenia.

Again, this has to do with the fact that deleterious mutations are far more common (it's much easier to break something than improve it genetically) and the logistical factors involved in screening the population for beneficial mutations.

I've asked you before how you would screen contemporary populations for beneficial mutations related to their neural or brain functions and you had no answer. I doubt you have one now.

 

[Naraoia]

Or the most obvious reason given the relatively rarity of beneficial mutations combined with the logistical difficulties in screening for such mutations means they just haven't been found yet.

Indeed, that's a good point. Challenge for those who aren't too lazy to dig through the literature: anyone has a few brain development-related polymorphisms where one version makes you brainier but the other doesn't make you retarded either? (Preferably the better version should also be the rarer so we can be more certain that it is indeed the novel mutation rather than the 'wild type')

 

[Naraoia]

BTW, Pete, consider yourself repped

 

[Loudmouth]

That does it LM, I'm really done playing with you.

This is what I said:

Let's try this one more time since you choose to be curt and condescending about all of this. When the known divergence goes from 1.33% to 5% doesn't that make the mutation rate well beyond what happens in reality?

I was talking about the "curt and condescending" comment. I thought it was quite ironic that you were accusing others of being condescending when you are consistently condescending to others. Hence the "Pot meet Kettle" reference.

Just one more time, what is the difference in human DNA when directly compared to that of the chimpanzee?

About 1-2% difference in DNA that they share through common ancestry and 5% if indels are considered. It all depends on the context of the comparison, something that you have yet to understand.

 

[mark kennedy]

Please dear, if you argue a point then it is you who must come up with relevant supporting examples. I'm not acting as if that's difficult, I'm acting as if you've not done your job.

The regulatory gene HAR1f is one example among many of unique human genes involved in the development of the brain. I have no special interest in RNA non-coding genes but that was an extraordinary example of a region that would have had to undergo a massive overhaul.

You seem to want to focus on RNA, I think I can work with that.

Ok, the infamous P53 sort-of fits. (Though it's still not an RNA gene, as you may have noticed...)

And the mutations you quote are tandem repeat polymorphisms. Of 68 bases. Hardly a point mutation. Might be called a large indel but it's certainly not on the scale of the mutations in the brainy gene you were originally talking about.

Ok, you are wanting to talk about non-coding RNA genes and point mutations. That's pretty specific but intriguing.

Besides, it's still not an RNA gene. (Which is perhaps the lesser of my peeves, but still, if you want to say something about an RNA gene then please support what you say with RNA gene examples if at all possible)

If that's what you want to focus on, I don't see why not.

No, you have given examples of deleterious mutations (most of which were pretty large ones). If you could cite, say, a respectable enough review article or database thing or something that says there are no known beneficial mutations and provides some support other than a few genetic diseases I'd be more inclined not to dismiss your argument.

There is nothing in scientific literature saying there are any affects other then deleterious. I research this regularly and I am not exaggerating when I say the examples of disease and disorder are legion while beneficial affects are non-existent.

Honestly I don't know if you are just putting me on, running me in circles or simply wanting to focus on a narrow range of details. I would suggest we take a look at this:

Abstract:

Increasing evidence suggests that the development and function of the nervous system is heavily dependent on RNA editing and the intricate spatiotemporal expression of a wide repertoire of non-coding RNAs, including micro RNAs, small nucleolar RNAs and longer non-coding RNAs. Non-coding RNAs may provide the key to understanding the multi-tiered links between neural development, nervous system function, and neurological diseases.​

Non-coding RNAs in the nervous system, J Physiol. 2006 September 1

I'll try to keep this somewhat brief since I realize that not everyone on here is just bored stiff looking for something to do. They discuss different non-coding RNA genes but just look at what they say in the opening two paragraphs:

The nervous system is unique among organs in its precise and sophisticated patterns of regional cellular morphogenesis, cellular diversity, membrane electrical properties, responses to changing environmental inputs and perturbations, neural network connections, and dynamic activity-dependent alterations in synaptic strength underlying higher order cognitive functions including learning and memory (Abrous et al. 2005). These functional properties are, in turn, orchestrated by a corresponding set of multilayered developmental mechanisms (Mehler, 2002a, b), including neural induction, neural patterning and axis formation within the evolving neural plate and neural tube, elaboration of stem cell generative zones throughout the neuraxis and the evolution of connections between specialized regional neuronal and glial cell types.

Alterations of specific components of these developmental stages and maturational processes result in a broad spectrum of neurodevelopmental disorders and predispose to an equally complex array of adult neurological and neuropsychiatric disorders of unknown aetiology, underscoring the levels of complexity in developmental and mature brain–behaviour relationships. However, we have little understanding of the genetic programs and molecular mechanisms that orchestrate nervous system development, plasticity and function, or how these programs and mechanisms are perturbed in disease.​

Isn't that what you asked for when you said:

If you could cite, say, a respectable enough review article or database thing or something that says there are no known beneficial mutations

If you think I have a long list of diseases and disorders try scanning that article. They will tell you that, 'these programs and mechanisms are perturbed in disease' and proceed to give you a long list of them.