"Why does superstition run so rampant in my Imperium that an entire Founding of Space Marine chapters is literally named 'cursed' in its official descriptors, as if a cabal of fucking wizards put a spell on it?"
"Is that really so unlikely, my lord?"
- – The Emperor and a Custodian, discussing the details of this founding... and displaying a keen level of understanding of the universe they live in.
One of the many Space Marine Chapter Foundings since the Legions were created for the Great Crusade. This one in particular is noteworthy because it was the largest since the Second Founding, and also called the Cursed Founding.
Fresh with the start of the 36th Millennium, five millennia after the First Founding, the Adeptus Mechanicus felt that it was about time to tinker with the gene-seed of the new Chapters and correct the many errors that had accumulated over the centuries.
Even when the Mechanicus managed to avoid creating mutated Chapters, it seems that their other creations were cursed with bad luck. For example, the Fire Hawks became the Legion of the Damned after they were lost in the Warp (maybe), and the Lamenters, who apparently managed to end up cured of the Black Rage and Red Thirst, are apparently the most disaster-prone Chapter in the Imperium, and then turned out to fall to the Black Rage anyway. Only three canon chapters seem to be doing pretty well: the Black Dragons, who the Inquisition wants to erase in the same way as the Flame Falcons, the Minotaurs, who are the Space Marine-killing headsmen of the High Lords of Terra that may not even be the original Chapter, and the Sons of Antaeus, who are confirmed as being active as late as M41.9, with at least one of them being a member of Deathwatch. (Well, four if you count the Lamenters, at least they're still alive...)
Several active traitor warbands, especially the Blood Gorgons are alive and kicking (even if their author's career isn't) and pretty awesome, too, but, you know, evil chaos men and stuff. They were declared Excommunicate traitoris by the Inquisition; it's not clear if they actively opposed the Imperium, decided to just go and do their own thing, or were (this is perhaps very slightly implied) unjustly implicated and swept up in the whole scandal of the disaster that was the "cursed" founding to begin with.
Because of these many misfortunes, the 21st Founding has come to be known as the Cursed Founding. Those Chapters unfortunate enough to have been founded at this time are barely tolerated by the Inquisition, if at all, and are mostly shunned by the rest of the Imperium. It's not exactly known why the 21st founding was cursed of all things, but it was probably Tzeentch getting his dose of lulz. Given the extensive genetic engineering involved, it is also possible that Fabius Bile was somehow involved. Or perhaps, Belisarius Cawl was tinkering around.
On the tabletop
Fan-made chapters may also use this Founding to justify some peculiar genetic quirk.
It's called the cursed founding, by apparently introducing more mutations and flaws. However, how the fuck is creating the Legion of The Damned a bad thing? The Black Dragons got a kickass Wolverine thing (more like Baraka), among many other actual improvements.
...Oh right, mutations are synonymous with the involvement of Chaos. And the Legion only shows up extremely infrequently.
Actually, the Black Dragons and Legion of the Damned were a small amount of loyalist rarities in a large founding (the largest since the 2nd Founding). Although we're given only a small amount of specific examples, it's explicitly stated that the vast majority of Cursed Founding chapters fell to Chaos, went renegade, went INSANE, or had ridiculously bad luck and went extinct from it (the Lamenters apparently weren't the only ones. They're just the only ones that managed to survive in spite of it). And even the Black Dragons get a ton of crap to dodge in exchange for the advantages of their mutations. Not least Dark Eldar wanting them for science experiments.
Going to the "Primaris Beta Edition" theory, Cawl would brag about how his NuMarines were allegedly immune to the curses of their parent chapters (namely the Wulfen curse and, to an extent, the Red Thirst), but they still ended up exhibiting them anyway. The Primaris Geneseed also saw the return of some organs that were either thought lost or malfunctional in a given chapter and its descendants, but none of the Cursed chapters with mutations have been "cured" by this method, with the Black Dragons and Lamenters getting Primaris forces as well. Compensation perhaps? Cawl pulling some strings to give them needed reinforcements? Farming "useful" mutations when need be? Who knows.
Yet another take is the "Minotaur Cover-up" angle. According to Eadwin Brown, one of the developers of the Badab War; the current-day Minotaurs were created from a group of repentant Iron Warriors who were allowed to rejoin the Imperium of Man as rather than out and out treason they were a distant garrison who missed out on the heresy and didn't manage to reestablish contact until the Great Scouring (essentially meaning they spent several years thinking that they were on a standard Great Crusade garrison posting, making them technically Traitor Legion Loyalists), but at the cost of changing their identity and being at the High Lords beck and call, which solves the mystery of their confusing history by playing it up as a cover-up. The theory is that in order to do this without getting the Inquisition breathing down their necks, the High Lords had to hastily create a justification for their sudden reappearance, and what better justification than the decision to "fix" flaws in other space marine chapters and declaring a new founding, meaning that there's a possibility that the Cursed Founding could have been cursed through the simple, ugly issues born of bureaucratic shell-shuffling. Indeed, the Minotaurs created during the 21st Founding (the old awful Mustard and Ketchup color scheme) were completely batshit insane berserkers, with the shuffling to the High Lords' (and perhaps unwittingly the Adeptus Custodes') anti-Astartes police makes it seem like they tossed in some leftover World Eater gene seed, made them Chimeras with some other gene seed and used the resulting ball of unstable psychosis to mutual kill something, then used the conveniently present Chapter to get the Iron Warrior Minotaurs legitimized (possibly keeping the World Eater-someone else Chimeras around under modern Minotaur colors as a tip-of-the-spear specialist force to unleash when Rip and Tear is needed before the rest of the Chapter spends precious gear).