I think you already know this, but there is a good bit of information for your family posted at the FamilySearch website, which shows Ellen Loftus, her mother Bridget Burke, and the various Holmes descendants whom you mentioned. FamilySearch is operated by the LDS church, and is free to use. The site is located here: https://www.familysearch.org ; The listing shows Bridget Burke as having been born in Mayo, but shows Elllen as being born in Ohio.
My assumption that you have been involved with the records there is because the site shows a Carrie Searcy as having input some of them. In case that is someone else, you can create an account there and acess the info. The database does not have separate family trees, and is essentially one huge tree of linked records, in which there is a single record for each person, with a unique identification number (although sometimes people unknowingly create duplicate records for the same person, which you can merge when you spot them). You can search by name, but also by that number, and the number for Ellen Loftus is 99PD-33G. Once you are at that record, you will see how easily you can move up and down the tree by clicking on the names of other people who are shown.
I may be able to supplement what you were given above, because I have Loftus and Brennan relatives from Mayo myself. They lived in East Mayo, in and around the parishes of Killassser (for the Loftus's), Killedan (Kiltimagh) and Bohola. You could focus initially on those parishes in your search, but (as already mentioned) those surnames were also found in a wider area of Mayo and in neighboring counties. I have no known Burke relatives in that area, but the Burke's were originally a Norman family (de Burgo) which ruled parts of Mayo (as well as other areas).
The Loftus surname originated in western Mayo, although it is now found in other parts of the county as well. There is/was an English family named Loftus, a few of whom did make it to Ireland, but most Irish people with the surname Loftus (still found principally in Mayo) originated as O’Loughnane's, from the Irish surname Ó Lachtnáin. Lachtnáin comes from an old word for the color grey, lachtna (in modern Irish, grey is liath), so it probably meant something like “descendant of the grey haired fellow” (the “Ó” part of the name means essentially “descendant”). As English-speakers took control in an area, many names were translated (often poorly) or converted to something easier for English speakers to spell or say, or were changed to an English name that sounded similar or had prestige. The change from O’Loughnane to Loftus is believed to be an example of a prestige name being used, although some O’Loughnane's ended up with the surname Grey, as a result of translation (and some stayed as O'Loughnane). Exactly when the changes took place is apparently unclear from the historical records
As mentioned above, the Brennan surname exists in several parts of Ireland. There were actually four main septs (tribes), unrelated to one another, all using the surname, but in each case the Irish form is Ó Braonáin. The Irish word braon has several meanings, but the surname is believed to derive from an old meaning of "sorrow", so the surname may originally have meant something like "descendant of the sorrowful one". Many surnames of Gaelic origin are derived from a nickname or characteristic of a real or legendary ancestor. The Ó Braonáin sept in Connacht (the West of Ireland) originated in East Galway, and the parishes in Mayo whichi I mentioned are located not too far from the border with that part of Galway.
Since you have Loftus's, originally from West Mayo, intermarrying with Brennan's, originally from East Galway, East Mayo is a reasonable guess for where the two families might have met.
