Environment and genetics

[Guest guest]

>

> " All of the above leads me to think, perhaps erroneously, that maybe

we

> shouldn't only be looking at environmental impact on autistics

directly, but

> also the effect of environment on their parents, which may have

created some

> mutations in the genes they then passed on. For instance, the

widespread

> introduction of unregulated pesticides in the 1940s. "

This is just what I wonder about.

>

> " Human DNA is constantly barraged by a variety of environmental

agents,

> including UV light and chemicals, as well as by reactive oxygen

species

> (ROS), which are produced as byproducts of normal metabolic

reactions or as

> molecular executors of host defense. These agents may cause the

nucleobases

> in DNA to spontaneously undergo a chemical transformation known as

> oxidation. 8-oxoG is an oxidized form of the common nucleobase

guanine (G),

> and when present in the genome, may form an unconventional base-

pair with

> adenine (A). When DNA replication occurs, the abnormally placed

adenine is

> paired with a thymine (T) instead of the original guanine, thereby

resulting

> in a permanent nucleobase change. "

This is very interesting. If true that the ability to detoxify is

impaired, free radicals and oxidation which cause damage are shown

here as changing DNA and causing permanent change.

[Guest guest]

Firstly, I am always a little cautious about broad statements about

genetics. It is an extremely complicated subject, not easily given to

formulistic shortcuts.

Take the following article, for example. It speaks of phenotypic variation,

which, while it may not be limited to heritability, it is a factor.

(but first, some definitions:

Phenotype

" 1 a.)The observable physical or biochemical characteristics of an organism,

as determined by both genetic makeup and environmental influences.

b.)The expression of a specific trait, such as stature or blood type,

based on genetic and environmental influences.

2. An individual or group of organisms exhibiting a particular phenotype "

Heritability

" In genetics, heritability is the proportion of phenotypic variation in a

population that is due to genetic variation. Variation among individuals may

be due to genetic and/or environmental factors. Heritability analyses

estimate the relative importance of variation in each of these factors.)

All of the above leads me to think, perhaps erroneously, that maybe we

shouldn't only be looking at environmental impact on autistics directly, but

also the effect of environment on their parents, which may have created some

mutations in the genes they then passed on. For instance, the widespread

introduction of unregulated pesticides in the 1940s.

FINALLY, the article that set me off about all this (yes, it is way over my

head too):

Environmental Triggers May Promote Human Genetic Variation

05/01/06 -- In this month's issue of the leading scientific journal Genome

Research, scientists from Kyushu University report how environmentally

damaged DNA may contribute to human genetic diversity. They describe the

co-occurrence of an aberrant nucleobase, called 8-oxoguanine (8-oxoG), with

genomic regions enriched in meiotic recombination " hotspots " and single

nucleotide polymorphisms (SNPs). The findings have implications for

understanding the interplay between heredity and the environment in shaping

human phenotypic variation.

Human DNA is constantly barraged by a variety of environmental agents,

including UV light and chemicals, as well as by reactive oxygen species

(ROS), which are produced as byproducts of normal metabolic reactions or as

molecular executors of host defense. These agents may cause the nucleobases

in DNA to spontaneously undergo a chemical transformation known as

oxidation. 8-oxoG is an oxidized form of the common nucleobase guanine (G),

and when present in the genome, may form an unconventional base-pair with

adenine (A). When DNA replication occurs, the abnormally placed adenine is

paired with a thymine (T) instead of the original guanine, thereby resulting

in a permanent nucleobase change.

One might intuitively expect the distribution of aberrant 8-oxoG nucleobases

to be randomly distributed throughout the genome, but in their new study,

Dr. Yusaku Nakabeppu and his colleagues demonstrated otherwise. Nakabeppu

teamed up with Drs. Mizuki Ohno and Tomofumi Miura, among others, to

investigate the distribution of 8-oxoG on spreads of normal human

chromosomes with fluorescently labeled antibodies that specifically attached

to 8-oxoG positions. Intriguingly, the dot-like fluorescent signals did not

cover the chromosomes uniformly but rather, exhibited a striking bias for

chromosomal regions that contain higher meiotic recombination rates and SNP

densities. Furthermore, the distribution and intensity of 8-oxoG was

remarkably similar in different individuals.

" We suggest that 8-oxoG accumulation in a particular region of a chromosome

causes meiotic recombination, " says Nakabeppu. " Our theory is supported by

studies showing that enzymes involved in the repair of oxidative DNA damage

can also induce homologous recombination. These enzymes are highly expressed

in the ovary and testis, where meiotic recombination normally occurs.

Furthermore, meiotic recombination rates in females are significantly higher

than in males, probably because oocytes are exposed to oxidative stress for

longer periods of time than are spermatocytes. "

The uneven distribution of SNPs across the human genome has been documented

for some time, but the causes of these nucleobase substitutions and the

factors determining their distribution are largely unknown. Nakabeppu,

therefore, also suggests that 8-oxoG, due to its mutagenic potential, may

contribute to the formation of SNPs.

But why the clustering of 8-oxoG?

" The factors determining the distribution of 8-oxoG are still unknown, "

explains Nakabeppu. " One can certainly argue that there must be another

factor that coincidentally increases the recombination rate or the formation

of SNPs in addition to the accumulation of 8-oxoG in a particular region of

the chromosome. The local structures of chromosomes and their replication or

transcription might help to determine the distribution of 8-oxoG, but

further analysis is required to fully understand the mechanistic

relationship between 8-oxoG, recombination, and mutagenesis. "

Source: Cold Spring Harbor Laboratory