genetika

• Fragile x mental retardation
• CG delka -> metylace -> inexpression
• V premutaci ataxie

• Matka imprintovany lokus, tatinek loss
• Overžrout, debil

Vsude po genomu, v intronech, guidují modifikacni proteiny na rRNA, taky μRNA

• Tata imprintovany lokus, mama loss
• Happy puppet, palce

• Genomic imprinting is an epigeneticphenomenon that causes genes to be expressed in a parent-of-origin-specific manner.[
• These epigenetic marks are established ("imprinted") in the germline(sperm or egg cells) of the parents and are maintained through mitotic cell divisions in the somatic cells of an organism.[9]

Jen otcovsky

tDMR, cDMR, dDMR, aDMR

Autospecifikace - zdroj signálu uvnitř buňky dán

Achindriplazie

Cancer inhibition

BMP4 non-neurulace = dermace, chorda blokuje

Porucha NOG - synfalangismus, synostosis

• Rozpad
• N-terminus + cholesterol
• Micelova proliferace - gradient
• i autokrině
• Dispatched
• Patched
• Smoothened
• Gli tf

Holopros., cyclopia, pohybový, končetiny, trávicí, bilateralia, cancers - metastázy

Shh břicho nervové soustavy

Záda nervového systému, navadeni axonu, záda všeho, vývoj soustav, kožní adnexa, somitace

Micelovy gradient

Non-canonic přestavba aktinu, regulace ER Ca

Wnt, bmp, fgfs,...

• Juxtakrinně
• Delta ligand na membráně souseda
• Proteolyticky odštěpí intracelularni doménu která je tf

• Binární diferenciace
• Somitogeneze, jednotlivé linie,...

• Notch spouští hes7
• Hes7 blokuje notch
• Notch degraduje

Hodiny notch pro somitaci

Circadian - key one

• Typically lysin,arginin positively charged na povrchu - nls
• LxxxLxxLxL - nes
• L lipofylic

• tf, kódován na y, spouští SOX9
• Sox = sry box
• Sox9 - diferenciace varlete (sertolli, leydig x folicular, thecal)
• testosteron, antimullerian
• Kofaktory - sf1 (tf), fgf9

Sox9 - V reakci na BMP transormace mesenchymalniho kondenzatu

Sry muže být crossingoverovan na x

• Tf family
• Oči, uši, krční páteř, játra, ledviny, ...

Diferenciace myocytu

Zrejme tak probiha i imprinting v gametach

Ridici epiblastovy tf, soucast iPSC koktejlu

• Stochasticka determinace - lateralni inhibice - oct8 epiblast
• Koncentracni gradient - shh skkerotom
• Reakcne difuzni mechanismus - wnt folikuly
• Molekularni hodiny - axin2 a lfng při somitaci
• Notch a hes7 ridi hodiny lfng
• Dale hodiny wnt

• Koduji homeodomain proteiny
• Homeodomain proteiny jsou specificka rodina tf - konzervativni sekvence amk napojujici se na dna - homeodoména
• Box znaci rodinu tf dle binding sekvence

Hox genes are thus a subset of the homeobox transcription factor genes

target genes of Hox genes promote cell division, cell adhesion, apoptosis, and cell migration.[21]

MicroRNA strands located in Hox clusters have been shown to inhibit more anterior hox genes ("posterior prevalence phenomenon"), possibly to better fine tune its expression pattern.[30]

In higher animals including humans, retinoic acid regulates differential expression of Hox genes along the anteroposterior axis.[33] Genes in the 3' ends of Hox clusters are induced by retinoic acid resulting in expression domains that extend more anteriorly in the body compared to 5' Hox genes that are not induced by retinoic acid resulting in expression domains that remain more posterior.

The reason for this colinearity is not yet completely understood, but could be related to the activation of Hox genes in a temporal sequence by gradual unpacking of chromatin along a gene cluster.


TAAT repetice v promotorech

• Vse funguje, jen pri meioze to ty gamety vzdaji a umrou, cili pak ani neprodukují hormony
• Předčasná ateroskleroza a osteoporoza

Porucha sekundární

• Himilogy x - nicméně bez c-o
• Centromera
• Dále orig muž:
• Amplifikace jednotlivých genů do rodin jako kompenzace crossoveru

• Diktyoten - dlouhý diploten
• Metafaze II skončí až po oplodnění

• Synistiza krania a prstů
• Apert - fgf2
• Acgindriplasia - fgf3
• Amolifikace sebe-podporou mutované spermatoginie

• Rozdílná expresivita a penetrance - 2 alely
• Rozdělení mozku na hemisféry - shh z prechordove ploténky

• Malformace - genetika
• Deformace - mechanika
• Dysplazie - histologicka úroveň
• Disrupce - zásah do normálního vývoje
• Sekvence - důsledky
• Asociace - bez příčinné souvislosti
• Syndrom - "známá kodifikovaná sekvence"?

• Nedostatek plodové vody
• Deformace

• Bones that breakeasily, blue tinge to the whites of the eye, short height, loose joints, hearing loss
• Dominant, collagen 1

• 30000 binding sequencies
• Insulator
• Homodimerisation - loops of code
• Binding to lamin
• Loops with cohesin - orientation
• Etc etc...

• Ctcf
• Cohesin
• Lamina binding

• HTH
• bHLH
• Zinc finger
• Homeobox
• bLZIP
• ...

Chromatin relaxation is one of the earliest cellular responses to DNA damage

Several in-vitro experiments suggest that ISWI remodelers organize nucleosome into proper bundle form and create equal spacing between nucleosomes, whereas SWI/SNF remodelers disorder nucleosomes.

The ISWI-family remodelers have been shown to play central roles in chromatin assembly after DNA replication and maintenance of higher-order chromatin structures.

INO80 and SWI/SNF-family remodelers participate in DNA double-strand break (DSB) repair and nucleotide-excision repair (NER) and thereby plays crucial role in TP53 mediated DNA-damage response.

NuRD/Mi-2/CHD remodeling complexes primarily mediate transcriptional repression in the nucleus and are required for the maintenance of pluripotency of embryonic stem cells.[13]

• Tumor suppressor
• These mutations act in a genetically dominant manner to alter chromatin regulatory function at enhancers[15]and promoters.[16]

adrenal glands, lungs

] In a recent study investigating correlations among maternal stress in pregnancy and methylation in teenagers and their mothers, it has been found that children of women who were abused during pregnancy were significantly more likely than others to have methylated glucocorticoid-receptor genes,[55] which in turn change the response to stress, leading to a higher susceptibility to anxiety.

DNMT3C catalyzes the methylation of promoters of transposable elements during early spermatogenesis, an activity shown to be essential for their epigenetic repression and male fertility

The cut-and-paste transposition mechanism of class II TEs does not involve an RNA intermediate. The transpositions are catalyzed by several transposase enzymes. Some transposases non-specifically bind to any target site in DNA, whereas others bind to specific target sequences. The transposase makes a staggered cut at the target site producing sticky ends, cuts out the DNA transposon and ligates it into the target site. A DNA polymerase fills in the resulting gaps from the sticky ends and DNA ligase closes the sugar-phosphate backbone

Metylace dna blokuje

Vyroba inzulinu z human mRNA

PKU matky poškozující geneticky zdraví plod

• Jeden fenotyp - více genů
• Hluchota